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Ibanoglu MC, Yildiz AG, Tatar OB, Seckin B, Cicek T, Engin-Ustun Y. A different approach to PCOS: evaluation of spermiogram results in male patients with a family history of PCOS. Gynecol Endocrinol 2025; 41:2501694. [PMID: 40418647 DOI: 10.1080/09513590.2025.2501694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 04/14/2025] [Accepted: 04/25/2025] [Indexed: 05/28/2025] Open
Abstract
OBJECTIVE The aim of this study was to investigate the possible influence of a family history of PCOS on male reproductive health by comparing the spermiogram parameters of patients diagnosed with a first-degree relative with PCOS with those of a control group without such a family history. METHODS This prospective study included 51 male participants aged 19-39 years, 25 of whom had a first-degree relative diagnosed with PCOS, while 26 formed the control group. Semen samples were collected and analyzed according to the World Health Organization (WHO) 2021 guidelines. RESULTS In this study, the spermiogram results of 51 patients aged between 19 and 39 years with a mean age of 31.50 ± 4.80 years were analyzed. The median sperm concentration (0.6 vs. 11.1 million/ml; p = 0.024) was significantly lower in the study group and the median total progressive motile sperm concentration (3.7 vs. 3.0 million/ml; p = 0.010) was significantly lower in the control group. Comorbidities were more common in the study group, including hair loss (64%; p < 0.001) and gynecomastia (25%; p = 0.008). Robust regression analysis revealed that semen concentration was significantly higher in subjects with dyslipidemia (+95.973 million/ml; p < 0.001), as was sperm motility (+49.081 units; p < 0.001) and TPMSC (+74.028 million/ml; p < 0.001). CONCLUSION Men with family history of PCOS have distinct reproductive and metabolic features, including lower median sperm concentration and higher incidence of alopecia and gynecomastia. Dyslipidemia significantly predicted improved sperm concentration and motility.
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Affiliation(s)
- Mujde Can Ibanoglu
- Department of Infertility, Ankara Etlik Zubeyde Hanım Women's Health Training and Research Hospital, Ankara, Turkey
| | - Ayse Gizem Yildiz
- Department of Infertility, Ankara Etlik Zubeyde Hanım Women's Health Training and Research Hospital, Ankara, Turkey
| | - Ozde Beren Tatar
- Department of Infertility, Ankara Etlik Zubeyde Hanım Women's Health Training and Research Hospital, Ankara, Turkey
| | - Berna Seckin
- Department of Infertility, Ankara Etlik Zubeyde Hanım Women's Health Training and Research Hospital, Ankara, Turkey
| | - Tufan Cicek
- Department of Urology, Ankara Etlik Zubeyde Hanım Women's Health Training and Research Hospital, Ankara, Turkey
| | - Yaprak Engin-Ustun
- Department of Infertility, Ankara Etlik Zubeyde Hanım Women's Health Training and Research Hospital, Ankara, Turkey
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Peng H, Ren J, Zhao Y, Fang X, Wang X, Liu C, Wan Z. Unraveling the Connection between PCOS and renal Complications: Current insights and Future Directions. Diabetes Res Clin Pract 2025; 224:112235. [PMID: 40334925 DOI: 10.1016/j.diabres.2025.112235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2025] [Revised: 04/24/2025] [Accepted: 05/05/2025] [Indexed: 05/09/2025]
Abstract
Polycystic ovary syndrome (PCOS) represents the most prevalent endocrine disorder among women of reproductive age, affecting approximately 5-18% of females worldwide. Characterized by irregular ovulation, hyperandrogenism, and polycystic ovaries, hyperandrogenism is the defining feature. Recent evidence highlights that, in addition to its notable reproductive and metabolic consequences, PCOS may also contribute to an elevated risk of renal complications. This increased risk is attributed to chronic low-grade inflammation, hormonal dysregulation, and disturbances in lipid metabolism inherent to the condition. However, the pathological mechanisms, clinical manifestations, and progression of secondary renal damage in this cohort remain insufficiently studied. This review consolidates current understanding of the relationship between PCOS and chronic kidney disease (CKD), aiming to clarify potential mechanisms by which PCOS may induce secondary renal dysfunction, encompassing both direct renal impairment and indirect damage mediated through systemic alterations. Furthermore, it advocates for comprehensive management strategies to mitigate renal risks in patients with PCOS, emphasizing the necessity of multidisciplinary approaches and further research to address these critical gaps.
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Affiliation(s)
- Haoyu Peng
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
| | - Junyi Ren
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Yang Zhao
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, China; Department of Health Management Center & Institute of Health Management, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Xinyi Fang
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Xiaoxiao Wang
- Department of Organ Transplantation, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Chi Liu
- Department of Nephrology, Sichuan Clinical Research Center for Kidney Disease, Sichuan Provincial People's Hospital, University of Electronic Science and Technology, Chengdu, China.
| | - Zhengwei Wan
- Department of Health Management Center & Institute of Health Management, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
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Wang J, Luo Y, Liu Y, Tang X, Gu J, Huang Z, Lv T, Luo J, Fang G. Network pharmacology and experimental validation to elucidate the mechanism of the treatment of polycystic ovary syndrome with insulin resistance by Resina Draconis. J Ovarian Res 2025; 18:108. [PMID: 40413545 PMCID: PMC12102831 DOI: 10.1186/s13048-025-01685-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Accepted: 05/02/2025] [Indexed: 05/27/2025] Open
Abstract
BACKGROUND Resina Draconis(RD) is a traditional Chinese medicine that activates blood circulation and removes blood stasis. Modern pharmacological studies have proved that RD has hypoglycaemic, pancreatic islets-protective, oestrogenic activity, anti-inflammatory, antibacterial and anti-tumour effects. Studies have shown that insulin resistance (IR) is the core pathological mechanism of polycystic ovary syndrome (PCOS), and RD can lower blood glucose to ameliorate IR, which has achieved significant results in the treatment of diabetes. However, the mechanism of action of RD in the treatment of PCOS-IR is still unclear. METHODS Network pharmacology analysis was used to predict the potential therapeutic targets of the active ingredients of RD. Experimental validation used a rat model of insulin resistance in PCOS; PCOS-IR symptoms were assessed, ovarian pathology was evaluated, and serum levels of insulin and sex hormones were determined. Expression levels of the PI3K, p-PI3K, Akt, p-Akt, GLUT4, FOXO3a, and P27 proteins were also measured in rat ovaries, along with mRNA expression levels of PI3K, Akt, GLUT4, FOXO3a, and P27. RESULTS Network pharmacological analyses indicated that the PI3K/Akt signalling pathway may play an important role in the treatment of PCOS-IR rats with RD. Experiments in PCOS-IR rats showed that RD significantly reversed insulin resistance, improved pathological changes in the ovaries, increased serum levels of follicle stimulating hormone (FSH) and estradiol (E2), and decreased levels of luteinizing hormone (LH), testosterone (T) and insulin. In addition, RD increased the levels of PI3K, p-PI3K, Akt, p-Akt and GLUT4, and decreased the levels of FOXO3a and P27 in the ovarian tissues of PCOS-IR rats, suggesting that RD may improve the symptoms of PCOS-IR in rats through the PI3K/Akt signalling pathway. CONCLUSION RD might improve insulin resistance and ovarian function in PCOS-IR by upregulating PI3K, p-PI3K, Akt, p-Akt and GLUT4 expression and downregulating FOXO3a and P27, thereby activating the PI3K/Akt signaling pathway. RD also regulated the LH/FSH ratio, increased E2 levels, reduced LH and T levels, and alleviated PCOS-IR symptoms in a rat PCOS-IR model.
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Affiliation(s)
- Jing Wang
- Guangxi Key Laboratory for Applied Fundamental Research of Zhuang Medicine-Key Laboratory Project under Guangxi Health Commission, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530001, China
- Guangxi Higher Education Key Laboratory for the Research of Du-related Diseases in Zhuang Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530200, China
- Health Science Center, Hubei Minzu University, Enshi, 445000, China
| | - Yehao Luo
- School of Second Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510000, China
| | - Yueting Liu
- Guangxi Key Laboratory for Applied Fundamental Research of Zhuang Medicine-Key Laboratory Project under Guangxi Health Commission, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530001, China
- Guangxi Higher Education Key Laboratory for the Research of Du-related Diseases in Zhuang Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530200, China
| | - Xiusong Tang
- Guangxi Key Laboratory for Applied Fundamental Research of Zhuang Medicine-Key Laboratory Project under Guangxi Health Commission, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530001, China
- Guangxi Higher Education Key Laboratory for the Research of Du-related Diseases in Zhuang Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530200, China
| | - Jianhui Gu
- Guangxi Key Laboratory for Applied Fundamental Research of Zhuang Medicine-Key Laboratory Project under Guangxi Health Commission, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530001, China
- Guangxi Higher Education Key Laboratory for the Research of Du-related Diseases in Zhuang Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530200, China
| | - Zheng Huang
- Guangxi Key Laboratory for Applied Fundamental Research of Zhuang Medicine-Key Laboratory Project under Guangxi Health Commission, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530001, China
- Guangxi Higher Education Key Laboratory for the Research of Du-related Diseases in Zhuang Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530200, China
| | - Ting Lv
- Guangxi Key Laboratory for Applied Fundamental Research of Zhuang Medicine-Key Laboratory Project under Guangxi Health Commission, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530001, China
- Guangxi Higher Education Key Laboratory for the Research of Du-related Diseases in Zhuang Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530200, China
| | - Jun Luo
- Information Technology Center, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530001, China.
| | - Gang Fang
- Guangxi Key Laboratory for Applied Fundamental Research of Zhuang Medicine-Key Laboratory Project under Guangxi Health Commission, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530001, China.
- Guangxi Higher Education Key Laboratory for the Research of Du-related Diseases in Zhuang Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530200, China.
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Du M, Ge H. A cohort study on the association between metabolic/inflammatory status and pregnancy complications in PCOS patients after IVF/ICSI treatment. Medicine (Baltimore) 2025; 104:e42481. [PMID: 40419888 DOI: 10.1097/md.0000000000042481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/28/2025] Open
Abstract
This study aims to explore the impact of insulin resistance and metabolic abnormalities on metabolic changes, inflammatory responses, and pregnancy complications during in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment in women with polycystic ovary syndrome (PCOS). A total of 100 PCOS patients who attended our hospital between February 2022 and February 2024, along with 100 control subjects with natural pregnancies, were included. Blood samples were analyzed for a range of parameters, including sex hormones (luteinizing hormone, follicle-stimulating hormone, estrogen, progesterone, testosterone, and prolactin), glycometabolism (fasting plasma glucose, fasting insulin, and homeostasis model assessment of insulin resistance), liver and kidney function (triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, creatinine, blood urea nitrogen, and uric acid), and inflammatory markers (C-reactive protein, interleukins [IL-2, IL-4, IL-6, IL-8, IL-12, and IL-18]). Changes in metabolic and inflammatory indicators were monitored throughout different pregnancy stages (early, mid, and late), and pregnancy outcomes, neonatal birth weight, and Apgar scores were recorded. The PCOS-IVF/ICSI group exhibited significantly higher levels of body mass index, systolic blood pressure, menstrual cycle irregularities, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and hormones (luteinizing hormone, follicle-stimulating hormone, estrogen, progesterone, and testosterone) compared to the natural pregnancy group (P < .05). Pregnancy metabolic analysis showed significantly elevated fasting plasma glucose, fasting insulin, and homeostasis model assessment of insulin resistance indices across all pregnancy stages in the PCOS group (P < .01). Inflammatory markers, including C-reactive protein, IL-2, IL-4, IL-6, IL-8, IL-12, and IL-18, were also significantly higher in the PCOS-IVF/ICSI group (P < .05). Pregnancy outcome analysis revealed that the PCOS-IVF/ICSI group had higher rates of miscarriage and pregnancy complications (P < .05), with no significant difference in preterm birth rates (P = .12). Neonatal birth weight and Apgar scores were slightly lower in the PCOS-IVF/ICSI group compared to the natural pregnancy group (P < .05). Compared to women with natural pregnancies, the PCOS-IVF/ICSI group showed increased risks of metabolic disorders, inflammatory responses, and pregnancy complications, with slightly poorer neonatal outcomes, suggesting a higher risk during pregnancy for PCOS patients.
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Affiliation(s)
- Mengmeng Du
- Yangzhou University, Yangzhou, China
- Department of Gynecology And Obstetrics, Taizhou People's Hospital, Taizhou, China
| | - Hongshan Ge
- Yangzhou University, Yangzhou, China
- Department of Gynecology And Obstetrics, Taizhou People's Hospital, Taizhou, China
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Jiang Y, Li D, Cao CC, Feng W, Liu R, Xu Y, Cao C. Clinical Significance of Skeletal Fat-to-Muscle Ratio in Idiopathic Hyperaldosteronism. Clin Endocrinol (Oxf) 2025. [PMID: 40391493 DOI: 10.1111/cen.15274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Revised: 04/29/2025] [Accepted: 05/08/2025] [Indexed: 05/21/2025]
Abstract
OBJECTIVE The objective of this study is to evaluate the correlation between the fat-to-muscle ratio (FMR) and insulin resistance (IR) with aldosterone production among patients with idiopathic hyperaldosteronism (IHA). METHODS Patients with primary aldosteronism were screened from those with secondary hypertension and then subtyped via adrenal venous sampling. A total of 199 patients with IHA and 186 with essential hypertension (EH) (controls) were studied. Baseline clinical characteristics, including data on diabetes and IHA, were collected. The FMR was evaluated based on the distribution of adipose tissue and muscle, measured by a body composition analyzer. RESULTS The prevalence of diabetes and prediabetes was significantly higher in patients with IHA compared to those with essential hypertension. IHA patients also had significantly higher hemoglobin A1c(HbA1c) levels, homeostatic model assessment of insulin resistance (HOMA-IR), and much lower quantitative insulin sensitivity check index scores than the EH group. FMR was positively associated with fasting insulin, HOMA-IR, aldosterone-to-renin ratio (ARR), and age. A higher FMR was linked to the prevalence of IHA, with a stepwise increase in risk observed from the lowest to the highest quartiles of FMR. Logistic regression analysis showed that both HOMA-IR and body mass index contributed to the elevated FMR. IHA may result from a substantial loss of muscle mass accompanied by fat accumulation. DISCUSSION In this retrospective study, our findings suggest that FMR could serve as a valuable metric for early intervention and comanagement strategies in patients at risk of sarcopenic obesity. This approach could help block the progression from aldosterone-producing cell clusters to IHA, potentially inhibiting aldosterone overproduction in such patients.
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Affiliation(s)
- Yuhe Jiang
- Business Analytics, College of Business, Macau University of Science and Technology, Macau, China
| | - Dan Li
- Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Cassie Chen Cao
- School of Information, University of Sheffield, South Yorkshire, The UK
| | - Wenjing Feng
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Ruidong Liu
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yinfei Xu
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Caixia Cao
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China
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Wang L, Jin Y, Zhi Y, Li Z, Wang M, Wang B, Wang X. Effects of melatonin in polycystic ovary syndrome: is there Hippo pathway crosstalk? J Ovarian Res 2025; 18:101. [PMID: 40369589 PMCID: PMC12076993 DOI: 10.1186/s13048-025-01642-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Accepted: 03/06/2025] [Indexed: 05/16/2025] Open
Abstract
OBJECTIVE Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder among reproductive women, characterized by hyperandrogenism, oligo-ovulation and polycystic ovarian morphology. Incorporating complementary medicine alongside traditional lifestyle therapies for PCOS may offer additional benefits for affected women. Melatonin (MT), a hormone secreted by the pineal gland, has emerged as a potential treatment for regulating ovarian function in PCOS. However, the specific effects and underlying mechanisms of MT on PCOS need to be elucidated. METHODS This review consolidates evidence from randomized controlled trials, original research articles, systematic reviews, and meta-analyses regarding MT supplementation in PCOS, with a particular focus on its interaction with the Hippo pathway, to provide a comprehensive overview of current knowledge. RESULTS Current evidence suggests that MT plays a role in modulating PCOS through various mechanisms and is associated with the Hippo pathway. However, several uncertainties and key limitations in the existing literature must be addressed before these treatments can be integrated into standard clinical practice. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Lijun Wang
- Department of Obstetrics and Gynecology, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, China
- Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, China
| | - Yuanyuan Jin
- Department of Obstetrics and Gynecology, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, China
- Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, China
| | - Yuanyuan Zhi
- Department of Obstetrics and Gynecology, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, China
- Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, China
| | - Zhenzhen Li
- Department of Pathology, Shandong Provincial Maternal and Child Health Care Hospital, Qingdao University, Jinan, 250014, China
| | - Meili Wang
- Department of Obstetrics and Gynecology, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, China
- Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, China
| | - Boda Wang
- Emergency Department, Xinji Town Central Health Center, Guanxian County, Liaocheng, 252500, China
| | - Xinbo Wang
- Department of Obstetrics and Gynecology, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, China.
- Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, China.
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Usatiuc LO, Pârvu M, Pop RM, Uifălean A, Vălean D, Surd A, Țicolea M, Hîruța A, Ranga F, Cătoi FA, Cătană C, Pârvu AE. Therapeutic Potential of Lythrum salicaria L. Ethanol Extract in Experimental Rat Models of Streptozotocin-Induced Diabetes Mellitus and Letrozole-Induced Polycystic Ovary Syndrome. Antioxidants (Basel) 2025; 14:573. [PMID: 40427455 PMCID: PMC12108253 DOI: 10.3390/antiox14050573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2025] [Revised: 04/29/2025] [Accepted: 05/07/2025] [Indexed: 05/29/2025] Open
Abstract
Polycystic ovary syndrome (PCOS) and diabetes mellitus (DM) are prevalent endocrine disorders with overlapping pathophysiological mechanisms. Type 2 diabetes mellitus (T2DM) is commonly associated with PCOS, with both conditions strongly linked to insulin resistance (IR), while recent studies have also reported an increased prevalence of PCOS among women with type 1 diabetes mellitus (T1DM). This study evaluated the potential of Lythrum salicaria L. ethanol extract (LSEE) to mitigate oxidative stress (OS), inflammation, and metabolic and hormonal imbalances in separate experimental models of Streptozotocin (STZ)-induced DM and Letrozole (LET)-induced PCOS. LSEE underwent phytochemical analysis to quantify total phenolic and flavonoid content and HPLC-MS for polyphenols identification. In vitro, antioxidant capacity was investigated through FRAP, DPPH, NO, and H2O2 scavenging assays. Subsequently, in vivo, studies utilized STZ-induced DM and LET-induced PCOS rat models, with 10-day treatments of LSEE, metformin, or trolox (TX) administered by gavage. Dysregulation of hormonal profiles, ultrasound, and histological examinations confirmed PCOS development. At the end of the treatment period, serum samples were collected to assess OS markers (TOS, OSI, MDA, AOPP, 8-OHdG, NO, 3-NT, AGEs, TAR, SH) in both models. Inflammatory markers were also measured (IL-1β, NF-κB, IL-18, and Gasdermin D in DM and IL-1β, NF-κB, IL-18, and IL-10 in PCOS). Additionally, metabolic markers (glucose, lipids, TG-glucose index, liver enzymes) were assessed in DM rats, and hormones (LH, FSH, estrogen, testosterone, insulin, HOMA-IR) were determined in PCOS rats. LSEE demonstrated a high polyphenolic content and notable in vitro antioxidant activity. In vivo, it effectively reduced OS by lowering oxidant levels and enhancing antioxidant defenses, reduced inflammatory markers and blood glucose levels, and improved lipid profiles along with the TyG index and liver injury markers in diabetic rats. In PCOS rats, LSEE lowered the total oxidants, increased antioxidants, reduced LH, FSH, testosterone, and insulin, and increased estrogen levels. The effects exhibited a dose-dependent pattern, with higher doses producing more pronounced benefits comparable to those observed with metformin and TX. In conclusion, LSEE may be a promising complementary treatment for DM and PCOS.
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Affiliation(s)
- Lia Oxana Usatiuc
- Pathophysiology, Department 2—Functional Sciences, Faculty of Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (L.O.U.); (A.U.); (M.Ț.); (F.A.C.); (A.E.P.)
| | - Marcel Pârvu
- Department of Taxonomy, Faculty of Biology and Geology, “Babes-Bolyai” University, 400012 Cluj-Napoca, Romania;
| | - Raluca Maria Pop
- Pharmacology, Toxicology and Clinical Pharmacology, Department 2—Functional Sciences, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Ana Uifălean
- Pathophysiology, Department 2—Functional Sciences, Faculty of Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (L.O.U.); (A.U.); (M.Ț.); (F.A.C.); (A.E.P.)
| | - Dan Vălean
- Surgery Department, “Iuliu Haţieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - Adrian Surd
- Pediatric Surgery and Orthopedics, Department of Mother and Child, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - Mădălina Țicolea
- Pathophysiology, Department 2—Functional Sciences, Faculty of Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (L.O.U.); (A.U.); (M.Ț.); (F.A.C.); (A.E.P.)
| | - Ana Hîruța
- Pathology Department, University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca, 400372 Cluj-Napoca, Romania;
| | - Floricuța Ranga
- Food Science and Technology, Department of Food Science, University of Agricultural Science and Veterinary Medicine of Cluj-Napoca, 400372 Cluj-Napoca, Romania;
| | - Florinela Adriana Cătoi
- Pathophysiology, Department 2—Functional Sciences, Faculty of Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (L.O.U.); (A.U.); (M.Ț.); (F.A.C.); (A.E.P.)
| | - Corina Cătană
- Center for Biodiversity and Conservation, Faculty of Horticulture and Business in Rural Development, University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca, 400372 Cluj-Napoca, Romania;
| | - Alina Elena Pârvu
- Pathophysiology, Department 2—Functional Sciences, Faculty of Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (L.O.U.); (A.U.); (M.Ț.); (F.A.C.); (A.E.P.)
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Gkantzos A, Kalogiannis S, Deda O. The Role of Aromatic Amino Acids in Polycystic Ovary Syndrome through Patients' Blood Metabolic Profiling: A Systematic Review of the Past Five Years. J Proteome Res 2025; 24:2208-2221. [PMID: 40244806 PMCID: PMC12053951 DOI: 10.1021/acs.jproteome.4c00937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 03/03/2025] [Accepted: 04/07/2025] [Indexed: 04/19/2025]
Abstract
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women of reproductive age that encompasses a multitude of signs and symptoms, including hyperandrogenism, polycystic ovarian morphology, ovulatory dysfunction, and insulin resistance. The study aims to explore the role of aromatic amino acid (AAA) disorders in the syndrome. A systematic search on the databases Scopus, PubMed, and Google Scholar until 20 July 2024 over the past 5 years regarding metabolomic studies on PCOS patients' blood and the status of AAAs resulted in 12 related papers. Our review showed that AAA metabolic pathways are dysregulated, and their levels in the blood serum and plasma of PCOS patients in most studies are elevated due to inflammation and oxidative stress which, assisted by gut dysbiosis, give rise to insulin resistance that develops into PCOS. AAA abnormalities can also directly induce the defining symptoms of the syndrome through diminished neurotransmitter availability and impaired signaling. According to our review, AAA perturbations are detected in every stage of PCOS pathophysiology, making them valuable biomarkers for early diagnosis and management of the syndrome. Further investigation of the biological function, role, and impact of AAAs, probably alongside other metabolites, including BCAAs, could lead to the discovery of new tools for preventing and managing PCOS symptoms.
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Affiliation(s)
- Apostolos Gkantzos
- Department
of Nutritional Sciences and Dietetics, International
Hellenic University, 57400 Thessaloniki, Greece
| | - Stavros Kalogiannis
- Department
of Nutritional Sciences and Dietetics, International
Hellenic University, 57400 Thessaloniki, Greece
| | - Olga Deda
- Laboratory
of Forensic Medicine & Toxicology, Department of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
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Li L, Mo Y, Yu X, He B, Dai Y, Fan L, Yang S, Liu H. Causal relationship between immune cells, metabolites and polycystic ovary syndrome identified by Mendelian randomization and mediation analyses. Immunol Cell Biol 2025; 103:461-472. [PMID: 40135765 DOI: 10.1111/imcb.70016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 12/24/2024] [Accepted: 02/26/2025] [Indexed: 03/27/2025]
Abstract
Immune cells and blood metabolites play essential roles in the development of polycystic ovary syndrome (PCOS); however, it remains unclear whether blood metabolites mediate the causal relationship between immune cells and PCOS. This study aimed to delineate the causal relationships among immune cells, PCOS and potential blood metabolites through Mendelian randomization (MR). A two-sample MR analysis was conducted using inverse variance weighting as the primary method to determine the causation between immune cells and PCOS risk. This was supplemented by a two-step MR analysis to assess the mediating role of blood metabolites between immune cells and PCOS. In addition, a series of sensitivity analysis methods were employed to test the robustness of the results. We also performed a reverse MR to evaluate the possibility of reverse causal relationships. Our findings identified 22 immune cell phenotypes causally linked to PCOS, with 12 acting as risk factors and 10 as protective factors for PCOS. Furthermore, 45 blood metabolites or ratios were causally related to PCOS. Mediation analysis revealed that X-25519 levels mediated 9.2% of the causal relationship between the absolute count of CD28-CD25++ CD8br and PCOS. In addition, N-acetylglucosamine/n-acetylgalactosamine levels and adenosine 5'-monophosphate levels mediated 6.7% and -11.1%, respectively, in the causation between naive DN(CD4- CD8-) %T cell and PCOS. The aspartate-to-citrate ratio mediated 8.6% of the causal relationship between CD20- CD38- %B cells and PCOS. Finally, reverse MR studies did not identify any reverse causation between the 22 immune cell phenotypes and PCOS. This study elucidates the causal links between immune cells and PCOS, highlighting the potential roles of four blood metabolites in mediating the interaction between immune cells and PCOS, thus providing new targets for research and therapeutic interventions.
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Affiliation(s)
- Lan Li
- Gynecology Department, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
- College of lntegrative Medicine, Hunan University of Traditional Chinese Medicine, Changsha, Hunan, China
| | - Yang Mo
- College of lntegrative Medicine, Hunan University of Traditional Chinese Medicine, Changsha, Hunan, China
| | - Ximing Yu
- College of lntegrative Medicine, Hunan University of Traditional Chinese Medicine, Changsha, Hunan, China
| | - Bing He
- Gynecology Department, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Yue Dai
- Gynecology Department, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Longlong Fan
- Gynecology Department, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Sijie Yang
- College of lntegrative Medicine, Hunan University of Traditional Chinese Medicine, Changsha, Hunan, China
| | - Huiping Liu
- College of lntegrative Medicine, Hunan University of Traditional Chinese Medicine, Changsha, Hunan, China
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10
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Monney M, Mavromati M, Leboulleux S, Gariani K. Endocrine and metabolic effects of GLP-1 receptor agonists on women with PCOS, a narrative review. Endocr Connect 2025; 14:e240529. [PMID: 40066975 PMCID: PMC11949528 DOI: 10.1530/ec-24-0529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Revised: 03/01/2025] [Accepted: 03/11/2025] [Indexed: 03/14/2025]
Abstract
Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. This condition is associated with various hormonal, reproductive and metabolic alterations, including androgen excess, ovulatory disorders and a hyperinsulinemic state. A personalized therapeutic approach is necessary to improve PCOS, focusing on patients' main concerns, with the goal of addressing ovarian dysfunction, reducing hyperandrogenism and improving metabolic alterations, particularly through weight reduction. The therapeutic class of glucagon-like peptide-1 receptor analogues (GLP-1 RAs) represents an attractive option for PCOS due to its various beneficial effects, such as weight loss. In this review, we discuss the clinical and pathological aspects of PCOS, as well as the data and potential roles of GLP-1 RAs in managing this condition.
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Affiliation(s)
- Marine Monney
- Division of Endocrinology, Diabetes, Nutrition and Therapeutic Patient Education, Department of Medical Specialties, Geneva University Hospitals, Geneva, Switzerland
| | - Maria Mavromati
- Division of Endocrinology, Diabetes, Nutrition and Therapeutic Patient Education, Department of Medical Specialties, Geneva University Hospitals, Geneva, Switzerland
- Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Sophie Leboulleux
- Division of Endocrinology, Diabetes, Nutrition and Therapeutic Patient Education, Department of Medical Specialties, Geneva University Hospitals, Geneva, Switzerland
- Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Karim Gariani
- Division of Endocrinology, Diabetes, Nutrition and Therapeutic Patient Education, Department of Medical Specialties, Geneva University Hospitals, Geneva, Switzerland
- Faculty of Medicine, University of Geneva, Geneva, Switzerland
- Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland
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11
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Geng L, Yang X, Sun J, Ran X, Zhou D, Ye M, Wen L, Wang R, Chen M. Gut Microbiota Modulation by Inulin Improves Metabolism and Ovarian Function in Polycystic Ovary Syndrome. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2412558. [PMID: 40192074 PMCID: PMC12120758 DOI: 10.1002/advs.202412558] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 02/27/2025] [Indexed: 06/01/2025]
Abstract
The management of metabolic disorder associated with polycystic ovary syndrome (PCOS) has been suggested as an effective approach to improve PCOS which is highly involved with gut microbiota, while the underlying mechanism is unclear. Here, we investigated the role of inulin, a gut microbiota regulator, in the alleviation of PCOS. Our findings showed that inulin treatment significantly improved hyperandrogenism and glucolipid metabolism in both PCOS cohort and mice. Consistent with the cohort, inulin increased the abundance of microbial co-abundance group (CAG) 12 in PCOS mice, including Bifidobacterium species and other short-chain fatty acids (SCFAs)-producers. We further verified the enhancement of SCFAs biosynthesis capacity and fecal SCFAs content by inulin. Moreover, inulin decreased lipopolysaccharide-binding protein (LBP) and ameliorated ovarian inflammation in PCOS mice, whereas intraperitoneal lipopolysaccharide (LPS) administration reversed the protective effects of inulin. Furthermore, fecal microbiota transplantation (FMT) from inulin-treated patients with PCOS enhanced insulin sensitivity, improved lipid accumulation and thermogenesis, reduced hyperandrogenism and ovarian inflammatory response in antibiotic-treated mice. Collectively, these findings revealed that gut microbiota mediates the beneficial effects of inulin on metabolic disorder and ovarian dysfunction in PCOS. Therefore, modulating gut microbiota represents a promising therapeutic strategy for PCOS.
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Affiliation(s)
- Lulu Geng
- Centre for Assisted ReproductionShanghai Key Laboratory of Maternal‐Fetal MedicineShanghai Institute of Maternal‐Fetal Medicine and Gynecologic OncologyShanghai First Maternity and Infant HospitalSchool of MedicineTongji UniversityShanghai200092China
| | - Xin Yang
- Shanghai Innovation Center of TCM Health ServiceShanghai University of Traditional Chinese MedicineShanghai201203China
- Section of Endocrinology, Internal MedicineSchool of MedicineYale UniversityNew HavenCT06520USA
| | - Jiani Sun
- Centre for Assisted ReproductionShanghai Key Laboratory of Maternal‐Fetal MedicineShanghai Institute of Maternal‐Fetal Medicine and Gynecologic OncologyShanghai First Maternity and Infant HospitalSchool of MedicineTongji UniversityShanghai200092China
| | - Ximing Ran
- Department of Biostatistics and BioinformaticsRollins School of Public HealthEmory UniversityAtlantaGA30322USA
| | - Dan Zhou
- Centre for Assisted ReproductionShanghai Key Laboratory of Maternal‐Fetal MedicineShanghai Institute of Maternal‐Fetal Medicine and Gynecologic OncologyShanghai First Maternity and Infant HospitalSchool of MedicineTongji UniversityShanghai200092China
| | - Mingming Ye
- Centre for Assisted ReproductionShanghai Key Laboratory of Maternal‐Fetal MedicineShanghai Institute of Maternal‐Fetal Medicine and Gynecologic OncologyShanghai First Maternity and Infant HospitalSchool of MedicineTongji UniversityShanghai200092China
| | - Li Wen
- Section of Endocrinology, Internal MedicineSchool of MedicineYale UniversityNew HavenCT06520USA
| | - Ruirui Wang
- Shanghai Innovation Center of TCM Health ServiceShanghai University of Traditional Chinese MedicineShanghai201203China
- State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese MedicineShanghai University of Traditional Chinese MedicineShanghai201203China
| | - Miaoxin Chen
- Centre for Assisted ReproductionShanghai Key Laboratory of Maternal‐Fetal MedicineShanghai Institute of Maternal‐Fetal Medicine and Gynecologic OncologyShanghai First Maternity and Infant HospitalSchool of MedicineTongji UniversityShanghai200092China
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Ajorlouie Z, Moshkian P, Baghdadi G, Amiri R, Biglari F, Rahimlou M. The association between the Mediterranean Diet and the Prime Diet Quality Score and polycystic ovary syndrome: a case control study. BMC Nutr 2025; 11:80. [PMID: 40241157 PMCID: PMC12001616 DOI: 10.1186/s40795-025-01067-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Accepted: 04/07/2025] [Indexed: 04/18/2025] Open
Abstract
INTRODUCTION Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age, characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. This study aims to investigate the association between adherence to the Mediterranean Diet (Med-Diet) and the Prime Diet Quality Score (PDQS) and the risk of PCOS. METHOD This case-control study included 472 women aged 18-45, with 180 PCOS cases and 292 controls. PCOS diagnosis was based on the Rotterdam criteria. Dietary intake was assessed using a validated food frequency questionnaire, and adherence to the Med-Diet and PDQS was calculated. Statistical analyses included logistic regression to examine associations between diet quality and PCOS. RESULTS Higher adherence to both the Med-Diet and PDQS was significantly associated with lower odds of PCOS. Participants in the highest quartile of the Med-Diet score had a 41% reduced risk of PCOS in the crude model (OR = 0.59, 95% CI: 0.48-0.67) and a 32% reduced risk in the fully adjusted model (OR = 0.68, 95% CI: 0.57-0.79), after adjusting for potential confounders, including age, body mass index (BMI), physical activity, and total energy intake. Similarly, those in the highest PDQS quartile showed a 53% reduced risk in the crude model (OR = 0.47, 95% CI: 0.35-0.56) and a 43% reduced risk in the fully adjusted model (OR = 0.57, 95% CI: 0.44-0.68), accounting for the same confounders. CONCLUSION The findings suggest that higher adherence to the Med-Diet and PDQS is associated with a reduced risk of developing PCOS. Further research is warranted to explore the underlying biological mechanisms and to establish causality through prospective cohort studies and randomized controlled trials.
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Affiliation(s)
- Zeinab Ajorlouie
- Department of Midwifery, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Paniz Moshkian
- Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Ghazal Baghdadi
- Department of Nutrition, School of Public Health, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Roksaneh Amiri
- Department of Nutrition, School of Public Health, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Fereshteh Biglari
- Department of educational management, Zanjan university of medical science, Zanjan, Iran
| | - Mehran Rahimlou
- Department of Nutrition, School of Public Health, Zanjan University of Medical Sciences, Zanjan, Iran.
- Metabolic Diseases Research Center, Health and Metabolic Research Institute, Zanjan University of Medical Sciences, Zanjan, Iran.
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Rao M, Guo Z, Dong H, Ho CS, Chen X, Li J, Hong X, You Y, Hao Y, Hu P, She X, Yu Q. The calculated and the rapid equilibrium dialyzed human serum free testosterone by LC-MS/MS and their performances in PCOS diagnosis. Clin Chim Acta 2025; 571:120210. [PMID: 39988300 DOI: 10.1016/j.cca.2025.120210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 02/10/2025] [Accepted: 02/20/2025] [Indexed: 02/25/2025]
Abstract
OBJECTIVE To compare the calculated and the rapid equilibrium dialyzed (ED) human serum free testosterone (FT) by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and to explore their performances in polycystic ovary syndrome (PCOS) diagnosis. METHODS A rapid ED LC-MS/MS method for serum FT was established and validated for linearity, lower limit of the measuring interval (LLMI), imprecision, trueness, stability, dilution, matrix specificity and carryover. The validated ED LC-MS/MS (ED-FT) was compared with calculated LC-MS/MS method from Vermeulen's formula (cFT) for FT measurement in 139 PCOS patients and 100 healthy controls. The performances of total testosterone (TT), ED-FT and cFT by LC-MS/MS in PCOS diagnosis were investigated with the same cohorts. RESULTS The linearity range of ED-FT was 1.74-890 pmol/L, with a LLMI at 1.74 pmol/L. The intra-assay and inter-assay imprecision were < 3.8 % and < 5.9 %. The trueness was acceptable with recoveries of 92.9 %-108.2 %. The equilibrium dialysis time was 4 h. The two FT methods displayed systematic and proportional differences and cFT showed significant positive deviations compared to ED-FT. Receiver operating characteristic curve analysis proved that ED-FT outperformanced in PCOS diagnosis with the an area under the curve at 0.973, sensitivity of 89.93 % and specificity of 96.00 %. CONCLUSIONS This study established a rapid, accurate and sensitive ED LC-MS/MS method for serum FT. ED-FT is optimal compared to TT and cFT by LC-MS/MS in PCOS diagnosis.
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Affiliation(s)
- Menghua Rao
- Clinical Mass Spectrometry Center, Guangzhou KingMed Center for Clinical Laboratory Co., Ltd., Guangzhou International Bioisland, No.10 Luoxuan Third Road, Guangzhou City 510005 Guangdong Province, China; Kingmed College of Laboratory Medicine, Guangzhou Medical University, Panyu District, Guangzhou 511436 Guangdong Province, China
| | - Zaixin Guo
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Heng Dong
- Clinical Mass Spectrometry Center, Guangzhou KingMed Center for Clinical Laboratory Co., Ltd., Guangzhou International Bioisland, No.10 Luoxuan Third Road, Guangzhou City 510005 Guangdong Province, China; Kingmed College of Laboratory Medicine, Guangzhou Medical University, Panyu District, Guangzhou 511436 Guangdong Province, China
| | - Chung Shun Ho
- Biomedical Mass Spectrometry Unit, Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong
| | - Xiuru Chen
- Clinical Mass Spectrometry Center, Guangzhou KingMed Center for Clinical Laboratory Co., Ltd., Guangzhou International Bioisland, No.10 Luoxuan Third Road, Guangzhou City 510005 Guangdong Province, China; Kingmed College of Laboratory Medicine, Guangzhou Medical University, Panyu District, Guangzhou 511436 Guangdong Province, China
| | - Jin Li
- Clinical Biochemistry and Immunology Testing Center, Guangzhou KingMed Center for Clinical Laboratory Co., Ltd., Guangzhou International Bioisland, No.10 Luoxuan Third Road, Guangzhou City 510005 Guangdong Province, China
| | - Xinyu Hong
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Yang You
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Yanfang Hao
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Pan Hu
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Xuhui She
- Clinical Mass Spectrometry Center, Guangzhou KingMed Center for Clinical Laboratory Co., Ltd., Guangzhou International Bioisland, No.10 Luoxuan Third Road, Guangzhou City 510005 Guangdong Province, China; Kingmed College of Laboratory Medicine, Guangzhou Medical University, Panyu District, Guangzhou 511436 Guangdong Province, China.
| | - Qi Yu
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
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14
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Ernest DK, Collier A, Chandrasekhar A, Xie L, Darraji S, Patel J, Almandoz JP, Messiah SE. Association of Polycystic Ovarian Syndrome Features and Metabolic Syndrome Among Reproductive-Aged Women in the United States. WOMEN'S HEALTH REPORTS (NEW ROCHELLE, N.Y.) 2025; 6:431-441. [PMID: 40308359 PMCID: PMC12040555 DOI: 10.1089/whr.2024.0143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/07/2025] [Indexed: 05/02/2025]
Abstract
Background Polycystic ovarian syndrome (PCOS) is associated with the metabolic health of racially and ethnically diverse women globally, but limited research exists on the association of PCOS and metabolic syndrome (MetS) among women in the United States. Objective To examine the association of PCOS features and MetS in a racially/ethnically diverse population of reproductive-aged women in the United States. Methods Cross-sectional data from 2,172 women (12-49 years) from the 2011-2016 National Health and Nutrition Examination Survey were analyzed. Univariate logistic regression models determined unadjusted associations of MetS and its components (elevated central obesity, glucose, blood pressure and triglyceride, and low high-density lipoprotein cholesterol) with PCOS features (log-transformed total testosterone (LTT), sex-hormone binding globulin (LSHBG), amenorrhea, and oral contraceptive pills (OCP) use). Multivariable logistic models examined age-adjusted associations stratified by race and ethnicity. Results The analytical sample (mean age = 30.3 years, 59% non-Hispanic White, 12.4% non-Hispanic Black, 18.7% Hispanic/Latina, 6.2% non-Hispanic Asian, 3.7% Other/multi-race) had a MetS prevalence of 14.5%. Overall, MetS was associated with age, body mass index, race/ethnicity, LTT and LSHBG concentrations, amenorrhea, and OCP use (p < 0.01 for all), and many of the PCOS features were protective against individual MetS components. Most race/ethnicities showed significantly lower odds of MetS with an increase in LSHBG, with varying impacts on individual MetS features. Conclusions Findings suggest significant associations between PCOS features and MetS among a racially and ethnically diverse population of reproductive-aged women in the United States. More robust and longitudinal studies are needed to further understand the underlying mechanism linking PCOS and MetS.
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Affiliation(s)
- Deepali K. Ernest
- Department of Epidemiology, School of Public Health, University of Texas Health Science Center at Houston (UTHealth), Houston, Texas, USA
| | - Asha Collier
- School of Human Ecology, University of Texas at Austin, Austin, Texas, USA
| | - Aparajita Chandrasekhar
- Department of Epidemiology, School of Public Health, University of Texas Health Science Center at Houston (UTHealth), Houston, Texas, USA
| | - Luyu Xie
- Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | | | - Jenil Patel
- Department of Epidemiology, School of Public Health, University of Texas Health Science Center at Houston (UTHealth), Houston, Texas, USA
- School of Public Health, UTHealth at Houston, Dallas, Texas, USA
| | - Jaime P. Almandoz
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Sarah E. Messiah
- Peter O’Donnell Jr School of Public Health, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
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15
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Lin L, Shen H, Wang Y. Mendelian randomization study showed no causality between metformin treatment and polycystic ovary syndrome. PLoS One 2025; 20:e0321380. [PMID: 40179096 PMCID: PMC11967963 DOI: 10.1371/journal.pone.0321380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 03/05/2025] [Indexed: 04/05/2025] Open
Abstract
BACKGROUND Despite previous clinical studies providing some evidence of an association between metformin treatment and polycystic ovary syndrome(PCOS), these findings remain controversial. To investigate whether the association reflect causality, a two-sample Mendelian randomization (MR) method was conducted. METHODS Data from genome-wide association studies were analyzed, with the exposure factor being metformin and the outcome variable being PCOS. The inverse variance weighted(IVW) was used as the primary method for MR analysis. In addition, MR-Egger, weighted median, heterogeneity tests, and sensitivity analyses were performed. RESULTS The initial and validation MR analyses indicated that genetically predicted metformin treatment had no effects on PCOS. Sensitivity analyses provided additional confirmation of the reliability of the MR results. CONCLUSIONS Our two-sample MR analysis did not find genetic evidence supporting a significant association between metformin treatment and PCOS.
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Affiliation(s)
- Liting Lin
- Reproductive Medical Center, Peking University People’s Hospital, Peking University, Beijing, China
| | - Huan Shen
- Reproductive Medical Center, Peking University People’s Hospital, Peking University, Beijing, China
| | - Yanbin Wang
- Reproductive Medical Center, Peking University People’s Hospital, Peking University, Beijing, China
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16
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Moradi R, Kashanian M, Yarigholi F, Pazouki A, Sheikhtaheri A. Predicting pregnancy at the first year following metabolic-bariatric surgery: development and validation of machine learning models. Surg Endosc 2025; 39:2656-2667. [PMID: 40064691 DOI: 10.1007/s00464-025-11640-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 02/21/2025] [Indexed: 03/26/2025]
Abstract
BACKGROUND Metabolic-bariatric surgery (MBS) is the last effective way to lose weight whom around half of the patients are women of reproductive age. It is recommended an interval of 12 months between surgery and pregnancy to optimize weight loss and nutritional status. Predicting pregnancy up to 12 months after MBS is important for evaluating reproductive health services in bariatric centers; therefore, this study aimed to present a prediction model for pregnancy at the first year following MBS using machine learning (ML) algorithms. METHODS In a nested case-control study of 473 women with a history of pregnancy after MBS during 2009-2023, predisposing factors in pregnancy within 12 months after MBS were identified and subsequently, several ML models, including the classification algorithms and decision trees, as well as regression analyses, were applied to predict pregnancy up to 12 months after MBS. RESULTS The highest area under the curve (AUC) was 0.920 ± 0.014 (95%CI 0.906, 0.927) for the C5.0 decision tree with sensitivity and specificity of 0.762 ± 0.044 (95%CI 0.739, 0.801) and 0.916 ± 0.028 (95%CI 0.883, 0.922), respectively. This model considered thirteen important factors to predict pregnancy at the first 12 months following MB, including menstrual irregularity, marital status, a history of abnormal fetal development, age, infertility type, parity, gravidity, fertility treatment, presurgery body mass index (BMI), infertility, infertility duration, polycystic ovary syndrome (PCOS), and type 2 diabetes (T2DM). CONCLUSION Developing the ML models, which predict pregnancy within 12 months after MBS, can help bariatric surgeons and obstetricians to prevent and manage suboptimal surgical response and adverse pregnancy outcomes.
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Affiliation(s)
- Raheleh Moradi
- Minimally Invasive Surgery Research Center, Iran University of Medical Sciences, Tehran, Iran.
| | - Maryam Kashanian
- Department of Obstetrics & Gynecology, Akbarabadi Teaching Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Fahime Yarigholi
- Division of Minimally Invasive and Bariatric Surgery, Minimally Invasive Surgery Research Center, Hazrat-E Fatemeh Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Abdolreza Pazouki
- Division of Minimally Invasive and Bariatric Surgery, Minimally Invasive Surgery Research Center, Hazrat-E Fatemeh Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Abbas Sheikhtaheri
- Department of Health Information Management, School of Health Management and Information Sciences, Iran University of Medical Sciences, Tehran, Iran.
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Kumbhar PS, Chavan R, Darekar S, Kolekar K, Sequeira A, Vishwas S, Gupta G, Paudel KR, Singh SK, Dua K, Disouza J, Patravale V. Bridging gap in treatment of polycystic ovarian syndrome through drug repurposing: what we achieved and where we are? NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:3213-3240. [PMID: 39520555 DOI: 10.1007/s00210-024-03578-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 10/28/2024] [Indexed: 11/16/2024]
Abstract
Polycystic ovarian syndrome (PCOS) is one of the chief causes of infertility in women of reproductive age. Several drugs belonging to the oral contraceptive class have been approved for the treatment of PCOS. Nonetheless, the capability to target only a few symptoms of PCOS and fatal side effects are key hurdles to their use. Therefore, repurposing existing drugs can be promising in managing PCOS efficiently. Drugs from different pharmacological classes like antidiabetics (metformin, rosiglitazone, pioglitazone, and semaglutide), statins (simvastatin and atorvastatin), antiandrogen drugs (finasteride and flutamide), etc. demonstrated significant potential in managing PCOS. The present review offers a comprehensive overview of all the medications examined as potential repurposed options for the efficient treatment of PCOS. The pathogenesis of PCOS, existing therapies for PCOS and their challenges, drug repurposing and its significance is also explained. The small-molecular drugs from various pharmacological classes and different phytoceuticals repurposed against PCOS are discussed along with their anti-PCOS activity mechanisms. Moreover, novel drug targets responsible for PCOS and opportunities for drug repurposing are briefed. The repurposed drugs in clinical trials for PCOS and drug repurposing challenges are discussed. Thus, drug repurposing can serve as a potential way to effectively treat PCOS, reducing the extent of infertility and improving the quality of life of women.
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Affiliation(s)
- Popat S Kumbhar
- Department of Pharmaceutics, Tatyasaheb Kore College of Pharmacy, Warananagar, Panhala, Kolhapur, Maharashtra, 416 113, India
| | - Revati Chavan
- Department of Pharmaceutics, Tatyasaheb Kore College of Pharmacy, Warananagar, Panhala, Kolhapur, Maharashtra, 416 113, India
| | - Snehal Darekar
- Department of Pharmaceutics, Tatyasaheb Kore College of Pharmacy, Warananagar, Panhala, Kolhapur, Maharashtra, 416 113, India
| | - Kaustubh Kolekar
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 144 411, India
| | - Anvitha Sequeira
- KLE College of Pharmacy, Nehru Nagar, Belagavi, Karnataka, 590010, India
| | - Sukriti Vishwas
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 144 411, India
| | - Guarav Gupta
- Center for Global Health Research (CGHR), Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai, India
- Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
| | - Keshav Raj Paudel
- Centre for Inflammation, Faculty of Science, School of Life Sciences, Centenary Institute and University of Technology Sydney, Sydney, NSW, 2007, Australia
| | - Sachin Kumar Singh
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 144 411, India.
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW, 2007, Australia.
- School of Medical and Life Sciences, Sunway University, 47500, Sunway City, Malaysia.
| | - Kamal Dua
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW, 2007, Australia
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW, 2007, Australia
| | - John Disouza
- Department of Pharmaceutics, Tatyasaheb Kore College of Pharmacy, Warananagar, Panhala, Kolhapur, Maharashtra, 416 113, India.
- SYBES's Bombay Institute of Pharmacy and Research, Dombivli (East), Maharashtra, 421204, India.
| | - Vandana Patravale
- Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai, Maharashtra, 400019, India.
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18
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Chen L, Hui L, Wang Y, Yao X, Li J. Elevated IGFBP7 expression in follicular granulosa cells promotes PCOS pathogenesis. Biochim Biophys Acta Mol Basis Dis 2025; 1871:167743. [PMID: 39988179 DOI: 10.1016/j.bbadis.2025.167743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Revised: 01/03/2025] [Accepted: 02/15/2025] [Indexed: 02/25/2025]
Abstract
Polycystic ovary syndrome (PCOS) can result in female infertility, menstrual irregularities, metabolic disturbances, hormonal imbalances, and significantly impact the reproductive health of women of childbearing age. Hyperandrogenism and insulin resistance are typical primary endocrine features of PCOS, which are also regarded as its core pathogenesis. In this study, IGFBP7 expression in granulosa cells (GCs) from women with and without PCOS was analyzed using bulk RNA-seq. A PCOS-like mouse model was constructed using dehydroepiandrosterone in IGFBP7 knockout and wild-type mice to explore the role of IGFBP7 in PCOS. Primary GCs from mice were cultured and transfected with IGFBP7 overexpression plasmid and siRNA fragments. Proliferation, apoptosis, and steroid hormone levels were measured to investigate the effects of IGFBP7 on granulosa cells. IGFBP7 expression was found to be elevated in patients with PCOS. Following IGFBP7 knockdown in mouse GC, there was a significant increase in GC proliferation, a decrease in GC apoptosis, and a notable decrease in testosterone secretion by GC. Conversely, overexpression of IGFBP7 in mouse granulosa cells significantly inhibited GC proliferation, significantly increased GC apoptosis, and led to a marked increase in testosterone secretion by GCs. With mouse model, a reduction in PCOS symptoms in mice after IGFBP7 deletion was observed. Elevated IGFBP7 expression in PCOS granulosa cells may induce apoptosis, hinder insulin signaling, and enhance androgen synthesis. These insights offer novel avenues for understanding and treating PCOS.
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Affiliation(s)
- Li Chen
- Department of Immunology, Center of Immunomolecular Engineering, Innovation & Practice Base for Graduate Students Education, Zunyi Medical University, Zunyi, China
| | - Linhu Hui
- Department of Immunology, Center of Immunomolecular Engineering, Innovation & Practice Base for Graduate Students Education, Zunyi Medical University, Zunyi, China
| | - Yongyang Wang
- Department of Immunology, Center of Immunomolecular Engineering, Innovation & Practice Base for Graduate Students Education, Zunyi Medical University, Zunyi, China
| | - Xinsheng Yao
- Department of Immunology, Center of Immunomolecular Engineering, Innovation & Practice Base for Graduate Students Education, Zunyi Medical University, Zunyi, China
| | - Jun Li
- Department of Immunology, Center of Immunomolecular Engineering, Innovation & Practice Base for Graduate Students Education, Zunyi Medical University, Zunyi, China.
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Pereira JD, Magalhães FMV, Tameirão FMS, Soriani FM, de O S Jorge KT, Reis FM, Cândido AL, Comim FV, Gomes KB. The possible regulatory role of miRNA-30c-5p, miRNA-545-3p and miRNA-125a-5p in women with polycystic ovary syndrome: A case-control study and signaling pathways. Mol Cell Endocrinol 2025; 599:112492. [PMID: 39952313 DOI: 10.1016/j.mce.2025.112492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 01/31/2025] [Accepted: 02/11/2025] [Indexed: 02/17/2025]
Abstract
INTRODUCTION Polycystic Ovary Syndrome (PCOS) is one of the most common endocrinopathy in women of reproductive age. MicroRNA (miRNAs) are small non-coding RNAs related to the control of gene expression in biological fluids. Our study analyzed the expression of miRNAs related to inflammation in individuals with PCOS compared to controls. METHODS Twenty patients with PCOS and 20 controls, matched by body mass index and age, were included in the study. The miRNAs evaluated were miRNA-30c-5p; miRNA-545-3p and miRNA-125a-5p. RESULTS The expression of the miRNAs was similar between the two groups. A positive correlation was observed between the expression of miRNA-125a-5p and LDLc levels only in the PCOS group. Subsequent analysis of biological pathways showed that miRNA-125a -5p is significantly involved in the regulation of SREBP/SREBF pathways of cholesterol biosynthesis, glycolysis, insulin receptor signaling, oxidative stress-induced senescence and estrogen-dependent gene expression. CONCLUSION The results suggest that the miRNA-125a-5p shows a potential implication to the regulation of lipid biosynthesis and LDL-c levels in PCOS women.
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Affiliation(s)
- Jessica D Pereira
- Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Fernanda M V Magalhães
- Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Fabiana M S Tameirão
- Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Frederico M Soriani
- Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Karina T de O S Jorge
- Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Fernando M Reis
- Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Ana Lúcia Cândido
- Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Fábio V Comim
- Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Karina B Gomes
- Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
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20
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Niinuma SA, Habib H, Takemoto ASN, Das P, Sathyapalan T, Atkin SL, Butler AE. A Cross-Sectional Exploratory Study of Rat Sarcoid (Ras) Activation in Women with and Without Polycystic Ovary Syndrome. Cells 2025; 14:377. [PMID: 40072105 PMCID: PMC11898917 DOI: 10.3390/cells14050377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 03/01/2025] [Accepted: 03/04/2025] [Indexed: 03/15/2025] Open
Abstract
Objective: Rat sarcoma (Ras) proteins, Kirsten, Harvey, and Neuroblastoma rat sarcoma viral oncogene homolog (KRAS, HRAS, and NRAS, respectively), are a family of GTPases, which are key regulators of cellular growth, differentiation, and apoptosis through signal transduction pathways modulated by growth factors that have been recognized to be dysregulated in PCOS. This study explores Ras signaling proteins and growth factor-related proteins in polycystic ovary syndrome (PCOS). Methods: In a well-validated PCOS database of 147 PCOS and 97 control women, plasma was batch analyzed using Somascan proteomic analysis for circulating KRas, Ras GTPase-activating protein-1 (RASA1), and 45 growth factor-related proteins. The cohort was subsequently stratified for BMI (body mass index), testosterone, and insulin resistance (HOMA-IR) for subset analysis. Results: Circulating KRas, and RASA1 did not differ between PCOS and control women (p > 0.05). EGF1, EGFR, and EGFRvIII were decreased in PCOS (p = 0.04, p = 0.04 and p < 0.001, respectively). FGF8, FGF9, and FGF17 were increased in PCOS (p = 0.02, p = 0.03 and p = 0.04, respectively), and FGFR1 was decreased in PCOS (p < 0.001). VEGF-D (p < 0.001), IGF1 (p < 0.001), IGF-1sR (p = 0.02), and PDGFRA (p < 0.001) were decreased in PCOS compared to controls. After stratifying for BMI ≤ 29.9 kg/m2, EGFR FGF8, FGFR1 VEGF-D, IGF1, and IGF-1sR differed (p < 0.05) though EGF1, EGFRvIII, FGF8, FGFR1, and VEGF-D no longer differed; after subsequently stratifying for HOMA-IR, only FGFR1, VEGF-D, IGF1, and IGF-1sR differed between groups (p < 0.05). Conclusions: Several growth factors that activate Ras differ between women with and without PCOS, and when stratified for BMI and HOMA-IR, only FGFR1, VEGF-D, IGF1, and IGF-1sR differed; these appear to be inherent features of the pathophysiology of PCOS.
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Affiliation(s)
- Sara Anjum Niinuma
- Research Department, Royal College of Surgeons of Ireland, Busaiteen, Adliya P.O. Box 15503, Bahrain; (S.A.N.); (H.H.); (A.S.-N.T.); (P.D.); (S.L.A.)
| | - Haniya Habib
- Research Department, Royal College of Surgeons of Ireland, Busaiteen, Adliya P.O. Box 15503, Bahrain; (S.A.N.); (H.H.); (A.S.-N.T.); (P.D.); (S.L.A.)
| | - Ashleigh Suzu-Nishio Takemoto
- Research Department, Royal College of Surgeons of Ireland, Busaiteen, Adliya P.O. Box 15503, Bahrain; (S.A.N.); (H.H.); (A.S.-N.T.); (P.D.); (S.L.A.)
| | - Priya Das
- Research Department, Royal College of Surgeons of Ireland, Busaiteen, Adliya P.O. Box 15503, Bahrain; (S.A.N.); (H.H.); (A.S.-N.T.); (P.D.); (S.L.A.)
| | - Thozhukat Sathyapalan
- Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull HU6 7RX, UK;
| | - Stephen L. Atkin
- Research Department, Royal College of Surgeons of Ireland, Busaiteen, Adliya P.O. Box 15503, Bahrain; (S.A.N.); (H.H.); (A.S.-N.T.); (P.D.); (S.L.A.)
| | - Alexandra E. Butler
- Research Department, Royal College of Surgeons of Ireland, Busaiteen, Adliya P.O. Box 15503, Bahrain; (S.A.N.); (H.H.); (A.S.-N.T.); (P.D.); (S.L.A.)
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21
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Rubino F, Cummings DE, Eckel RH, Cohen RV, Wilding JPH, Brown WA, Stanford FC, Batterham RL, Farooqi IS, Farpour-Lambert NJ, le Roux CW, Sattar N, Baur LA, Morrison KM, Misra A, Kadowaki T, Tham KW, Sumithran P, Garvey WT, Kirwan JP, Fernández-Real JM, Corkey BE, Toplak H, Kokkinos A, Kushner RF, Branca F, Valabhji J, Blüher M, Bornstein SR, Grill HJ, Ravussin E, Gregg E, Al Busaidi NB, Alfaris NF, Al Ozairi E, Carlsson LMS, Clément K, Després JP, Dixon JB, Galea G, Kaplan LM, Laferrère B, Laville M, Lim S, Luna Fuentes JR, Mooney VM, Nadglowski J, Urudinachi A, Olszanecka-Glinianowicz M, Pan A, Pattou F, Schauer PR, Tschöp MH, van der Merwe MT, Vettor R, Mingrone G. Definition and diagnostic criteria of clinical obesity. Lancet Diabetes Endocrinol 2025; 13:221-262. [PMID: 39824205 PMCID: PMC11870235 DOI: 10.1016/s2213-8587(24)00316-4] [Citation(s) in RCA: 108] [Impact Index Per Article: 108.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 09/15/2024] [Accepted: 10/07/2024] [Indexed: 01/20/2025]
Abstract
Current BMI-based measures of obesity can both underestimate and overestimate adiposity and provide inadequate information about health at the individual level, which undermines medically-sound approaches to health care and policy. This Commission sought to define clinical obesity as a condition of illness that, akin to the notion of chronic disease in other medical specialties, directly results from the effect of excess adiposity on the function of organs and tissues. The specific aim of the Commission was to establish objective criteria for disease diagnosis, aiding clinical decision making and prioritisation of therapeutic interventions and public health strategies. To this end, a group of 58 experts—representing multiple medical specialties and countries—discussed available evidence and participated in a consensus development process. Among these commissioners were people with lived experience of obesity to ensure consideration of patients’ perspectives. The Commission defines obesity as a condition characterised by excess adiposity, with or without abnormal distribution or function of adipose tissue, and with causes that are multifactorial and still incompletely understood. We define clinical obesity as a chronic, systemic illness characterised by alterations in the function of tissues, organs, the entire individual, or a combination thereof, due to excess adiposity. Clinical obesity can lead to severe end-organ damage, causing life-altering and potentially life-threatening complications (eg, heart attack, stroke, and renal failure). We define preclinical obesity as a state of excess adiposity with preserved function of other tissues and organs and a varying, but generally increased, risk of developing clinical obesity and several other non-communicable diseases (eg, type 2 diabetes, cardiovascular disease, certain types of cancer, and mental disorders). Although the risk of mortality and obesity-associated diseases can rise as a continuum across increasing levels of fat mass, we differentiate between preclinical and clinical obesity (ie, health vs illness) for clinical and policy-related purposes. We recommend that BMI should be used only as a surrogate measure of health risk at a population level, for epidemiological studies, or for screening purposes, rather than as an individual measure of health. Excess adiposity should be confirmed by either direct measurement of body fat, where available, or at least one anthropometric criterion (eg, waist circumference, waist-to-hip ratio, or waist-to-height ratio) in addition to BMI, using validated methods and cutoff points appropriate to age, gender, and ethnicity. In people with very high BMI (ie, >40 kg/m2), however, excess adiposity can pragmatically be assumed, and no further confirmation is required. We also recommend that people with confirmed obesity status (ie, excess adiposity with or without abnormal organ or tissue function) should be assessed for clinical obesity. The diagnosis of clinical obesity requires one or both of the following main criteria: evidence of reduced organ or tissue function due to obesity (ie, signs, symptoms, or diagnostic tests showing abnormalities in the function of one or more tissue or organ system); or substantial, age-adjusted limitations of daily activities reflecting the specific effect of obesity on mobility, other basic activities of daily living (eg, bathing, dressing, toileting, continence, and eating), or both. People with clinical obesity should receive timely, evidence-based treatment, with the aim to induce improvement (or remission, when possible) of clinical manifestations of obesity and prevent progression to end-organ damage. People with preclinical obesity should undergo evidence-based health counselling, monitoring of their health status over time, and, when applicable, appropriate intervention to reduce risk of developing clinical obesity and other obesity-related diseases, as appropriate for the level of individual health risk. Policy makers and health authorities should ensure adequate and equitable access to available evidence-based treatments for individuals with clinical obesity, as appropriate for people with a chronic and potentially life-threatening illness. Public health strategies to reduce the incidence and prevalence of obesity at population levels must be based on current scientific evidence, rather than unproven assumptions that blame individual responsibility for the development of obesity. Weight-based bias and stigma are major obstacles in efforts to effectively prevent and treat obesity; health-care professionals and policy makers should receive proper training to address this important issue of obesity. All recommendations presented in this Commission have been agreed with the highest level of consensus among the commissioners (grade of agreement 90–100%) and have been endorsed by 76 organisations worldwide, including scientific societies and patient advocacy groups.
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Affiliation(s)
- Francesco Rubino
- Metabolic and Bariatric Surgery, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London, UK; King's College Hospital, London, UK.
| | - David E Cummings
- University of Washington, Seattle, WA, USA; Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA
| | - Robert H Eckel
- University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Ricardo V Cohen
- Center for the Treatment of Obesity and Diabetes, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil
| | - John P H Wilding
- Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, UK
| | - Wendy A Brown
- Monash University Department of Surgery, Central Clinical School, Alfred Health, Melbourne, VIC, Australia
| | - Fatima Cody Stanford
- Neuroendocrine Unit, Division of Endocrinology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Division of Endocrinology, Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Rachel L Batterham
- International Medical Affairs, Eli Lilly, Basingstoke, UK; Diabetes and Endocrinology, University College London, London, UK
| | - I Sadaf Farooqi
- Institute of Metabolic Science and National Institute for Health and Care Research, Cambridge Biomedical Research Centre at Addenbrookes Hospital, Cambridge, UK
| | - Nathalie J Farpour-Lambert
- Obesity Prevention and Care Program, Department of Medicine, University Hospitals of Geneva, Geneva, Switzerland
| | - Carel W le Roux
- Diabetes Complications Research Centre, University College Dublin, Dublin, Ireland
| | - Naveed Sattar
- School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK
| | - Louise A Baur
- Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; Weight Management Services, The Children's Hospital at Westmead, Sydney, NSW, Australia
| | - Katherine M Morrison
- Centre for Metabolism, Obesity and Diabetes Research, Department of Pediatrics, McMaster University, Hamilton, ON, Canada; McMaster Children's Hospital, Hamilton, ON, Canada
| | - Anoop Misra
- Fortis C-DOC Center of Excellence for Diabetes, Metabolic Diseases and Endocrinology, New Delhi, India; National Diabetes Obesity and Cholesterol Foundation, New Delhi, India; Diabetes Foundation New Delhi, India
| | | | - Kwang Wei Tham
- Department of Endocrinology, Woodlands Health, National Healthcare Group, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Priya Sumithran
- Department of Surgery, School of Translational Medicine, Monash University, Melbourne, VIC, Australia; Department of Endocrinology and Diabetes, Alfred Health, Melbourne, VIC, Australia
| | - W Timothy Garvey
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
| | - John P Kirwan
- Pennington Biomedical Research Center, Baton Rouge, LA, USA
| | - José-Manuel Fernández-Real
- CIBER Pathophysiology of Obesity and Nutrition, Girona, Spain; Department of Medical Sciences, School of Medicine, University of Girona, Girona, Spain; Hospital Trueta of Girona and Institut d'Investigació Biomèdica de Girona, Girona, Spain
| | - Barbara E Corkey
- Chobanian & Avedisian School of Medicine, Boston University, Boston, MA, USA
| | - Hermann Toplak
- Division of Endocrinology and Diabetology, Department of Medicine, University of Graz, Graz, Austria
| | - Alexander Kokkinos
- First Department of Propaedeutic Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Robert F Kushner
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Francesco Branca
- Department of Nutrition and Food Safety, World Health Organization, Geneva, Switzerland
| | - Jonathan Valabhji
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK; Department of Diabetes and Endocrinology, Chelsea and Westminster Hospital National Health Service Foundation Trust, London, UK
| | - Matthias Blüher
- Helmholtz Institute for Metabolic, Obesity and Vascular Research of Helmholtz Munich, University of Leipzig and University Hospital Leipzig, Leipzig, Germany
| | - Stefan R Bornstein
- Department of Internal Medicine III, Carl Gustav Carus University Hospital Dresden, Technical University Dresden, Dresden, Germany; School of Cardiovascular and Metabolic Medicine & Sciences, Faculty of Life Sciences & Medicine, King's College London, London, UK
| | - Harvey J Grill
- Institute of Diabetes, Obesity and Metabolism, University of Pennsylvania, Philadelphia, PA, USA
| | - Eric Ravussin
- Pennington Biomedical Research Center, Baton Rouge, LA, USA
| | - Edward Gregg
- School of Population Health, Royal College of Surgeons in Ireland University of Medicine and Health Sciences, Dublin, Ireland; School of Public Health, Imperial College London, London, UK
| | - Noor B Al Busaidi
- National Diabetes and Endocrine Center, Royal Hospital, Muscat, Oman; Oman Diabetes Association, Muscat, Oman
| | - Nasreen F Alfaris
- Obesity Endocrine and Metabolism Center, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Ebaa Al Ozairi
- Clinical Research Unit, Dasman Diabetes Institute, Dasman, Kuwait
| | - Lena M S Carlsson
- Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Karine Clément
- Nutrition and Obesities: Systemic Approaches, NutriOmics Research Group, INSERM, Sorbonne Université, Paris, France; Department of Nutrition, Pitié-Salpêtrière Hospital, Assistance Publique-Hospital of Paris, Paris, France
| | | | - John B Dixon
- Iverson Health Innovation Research institute, Swinburne University of Technology, Melbourne, VIC, Australia
| | - Gauden Galea
- Regional Office for Europe, World Health Organization, Geneva, Switzerland
| | - Lee M Kaplan
- Section on Obesity Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - Blandine Laferrère
- Division of Endocrinology, Columbia University Irving Medical Center, New York, NY, USA
| | | | - Soo Lim
- Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seoul, South Korea
| | | | - Vicki M Mooney
- European Coalition for people Living with Obesity, Dublin, Ireland
| | | | - Agbo Urudinachi
- Department of Community Health, Alex Ekwueme Federal University Teaching Hospital Abakaliki, Abakaliki, Nigeria
| | - Magdalena Olszanecka-Glinianowicz
- Health Promotion and Obesity Management Unit, Department of Pathophysiology, Faculty of Medical Science, Medical University of Silesia, Katowice, Poland
| | - An Pan
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Francois Pattou
- Translational Research for Diabetes, Lille University, Lille University Hospital, Inserm, Institut Pasteur Lille, Lille, France; Department of General and Endocrine Surgery, Lille University Hospital, Lille, France
| | | | - Matthias H Tschöp
- Helmholtz Munich, Munich, Germany; Technical University of Munich, Munich, Germany
| | - Maria T van der Merwe
- University of Pretoria, Pretoria, South Africa; Nectare Waterfall City Hospital, Midrand, South Africa
| | - Roberto Vettor
- Internal Medicine, Center for the Study and the Integrated Treatment of Obesity, Department of Medicine, University of Padova, Padua, Italy; Center for Metabolic and Nutrition Related Diseases,Humanitas Research Hospital, Milan, Italy
| | - Geltrude Mingrone
- Division of Diabetes & Nutritional Sciences, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London, UK; Catholic University of the Sacred Heart, Rome, Italy; University Polyclinic Foundation Agostino Gemelli IRCCS, Rome, Italy
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Farhadi‐Azar M, Noroozzadeh M, Mousavi M, Saei Ghare Naz M, Ramezani Tehrani F. Impaired glucose tolerance and insulin resistance in a prenatally-androgenized rat model of polycystic ovary syndrome in later life. Exp Physiol 2025; 110:410-423. [PMID: 39613459 PMCID: PMC11868029 DOI: 10.1113/ep091912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 10/30/2024] [Indexed: 12/01/2024]
Abstract
Polycystic ovary syndrome (PCOS), one of the most common endocrine disorders in reproductive-aged women, is associated with metabolic disturbances. The present study aimed to examine changes in body weight (BW) and glucose and insulin tolerance in a prenatally-androgenized (PNA) rat model of PCOS compared to control with increasing age. Pregnant rats in the experimental group were subcutaneously injected with 5 mg of free testosterone on the 20th day of pregnancy, while the control group received the solvent. Female offspring of both groups, PNA rats (rat model of PCOS) and control, were examined in terms of changes in BW, glucose and insulin tolerance at 3, 6, 12 and 20 months of age. BW at birth (6.53 ± 0.89 vs. 5.60 ± 1.18 g; P = 0.038), 15 (25 ± 1.15 vs. 22.36 ± 3.98 g; P = 0.019) and 30 (59.37 ± 10.19 vs.49.9 ± 9.39 g; P = 0.022) days of age was significantly increased in the rat model of PCOS compared to control, but no significant differences were observed in BW of the rat model of PCOS compared to control at 60 (P = 0.155) and 75 (P = 0.932) days or at 3 (P = 0.239), 6 (P = 0.782), 12 (P = 0.755) and 20 (P = 0.092) months of age. Rat model of PCOS showed impaired glucose tolerance (IGT) at 3 months of age (P = 0.020) and insulin resistance (IR) with increasing age (3-20 months of age) compared to control. Increased BW before puberty, IGT at 3 months of age and IR with increasing age were observed in our rat model of PCOS. This rat model may contribute to a better understanding of underlying mechanisms of changes in BW, IGT and IR in future studies.
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Affiliation(s)
- Mahbanoo Farhadi‐Azar
- Reproductive Endocrinology Research Center, Research Institute for Endocrine SciencesShahid Beheshti University of Medical SciencesTehranIran
| | - Mahsa Noroozzadeh
- Reproductive Endocrinology Research Center, Research Institute for Endocrine SciencesShahid Beheshti University of Medical SciencesTehranIran
| | - Maryam Mousavi
- Reproductive Endocrinology Research Center, Research Institute for Endocrine SciencesShahid Beheshti University of Medical SciencesTehranIran
| | - Marzieh Saei Ghare Naz
- Reproductive Endocrinology Research Center, Research Institute for Endocrine SciencesShahid Beheshti University of Medical SciencesTehranIran
| | - Fahimeh Ramezani Tehrani
- Reproductive Endocrinology Research Center, Research Institute for Endocrine SciencesShahid Beheshti University of Medical SciencesTehranIran
- Foundation for Research & Education ExcellenceVestavia HillsALUSA
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23
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Li X, Cui Y, Zhang C, Zang W, Cheng Y, Yang C, Zhang S, Yu X, Gao L. Treatment of Qin Gui Wan (QGW) in PCOS abnormal oocytes development via AMPK/PGC-1ɑ pathway. JOURNAL OF ETHNOPHARMACOLOGY 2025; 342:119434. [PMID: 39894417 DOI: 10.1016/j.jep.2025.119434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 01/12/2025] [Accepted: 01/30/2025] [Indexed: 02/04/2025]
Abstract
OBJECTIVES To investigate the therapeutic effects of Qin Gui Wan (QGW) and its disassembled functional drug groups, Wenyang Zhuhuo (WYZH) and Xinwen Zhuyang (XWZY), on letrozole-induced PCOS rats. METHODS PCOS rat model was established by administering letrozole for 21 days. The rats were divided into control, PCOS, Diane-35, QGW, WYZH and XWZY groups. The changes of body weight, ovarian coefficient, estrous cycle and sex hormone levels were observed. The ovarian histological characteristics and ovulation were observed by HE staining. P450arom, SF-1, and AMPK/PGC-1ɑ pathway mRNA and protein expression were analyzed using qRT-PCR, WB, and IHC. The AMPK inhibitor Compound C (CC) was used to explore the treatment mechanism of QGW in granulosa cells. And UHPLC-MS/MS was used to performed chemical composition analysis. RESULTS QGW, WYZH, and XWZY can correct the disordered estrous cycle of PCOS rats and improve the serum hormone status of rats to varying degrees. HE results indicated that QGW, WYZH, and XWZY improved ovarian polycystic changes and normalized ovulation. qRT-PCR, WB, and IHC results demonstrated that QGW, WYZH, and XWZY increased PGC-1α, SF-1, and P450arom mRNA and protein expression in the ovaries of PCOS rats. The level of AMPK mRNA in the ovaries of QGW and its disassembled prescriptions increased, while only WYZH and XWZY rats showed increased ovarian AMPK levels. CC attenuated the activation of AMPK, PGC-1α, SF-1, and P450arom mRNA by QGW. CONCLUSIONS This study demonstrates that QGW alleviates abnormal oocyte development in PCOS rats, possibly by enhancing P450arom expression via the AMPK/PGC-1α pathway, thus restoring normal androgen-estrogen balance and follicular development.
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Affiliation(s)
- Xiaojuan Li
- Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Yiwei Cui
- Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Chuxin Zhang
- Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Weiyu Zang
- Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Yuli Cheng
- Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Chenyu Yang
- Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Shujing Zhang
- Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Xue Yu
- Beijing University of Chinese Medicine, Beijing, 100029, China.
| | - Lin Gao
- Beijing University of Chinese Medicine, Beijing, 100029, China.
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24
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Liu D, Liu D, Zhou K. Polycystic ovary syndrome and epithelial-mesenchymal transition: Mendelian randomization and single-cell analysis insights. J Ovarian Res 2025; 18:33. [PMID: 39972362 PMCID: PMC11841333 DOI: 10.1186/s13048-025-01617-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 02/04/2025] [Indexed: 02/21/2025] Open
Abstract
BACKGROUND The process of epithelial-mesenchymal transition (EMT) may promote fibrosis in ovarian tissue related to polycystic ovary syndrome (PCOS), thus affecting ovarian function and hormonal balance. OBJECTIVE This study aimed to explore key genes associated with EMT in PCOS and their potential molecular regulatory mechanisms, exclusively from the perspective of transcriptomics and single-cell RNA sequencing (scRNA-seq), combined with Mendelian Randomization (MR) analysis. METHODS The dataset for PCOS and EMT-related genes (EMT-RGs) were sourced from public databases. The key genes in this study were identified via differential expression analysis, MR, and evaluation of expression levels. Enrichment analysis and a series of functional analyses were conducted on these genes to further elucidate their potential mechanisms. Subsequently, using scRNA-seq data and validation of the expression of key genes, key cell group in PCOS were identified, followed by pseudo-time and cell communication analyses to provide deeper insights. RESULTS Three key genes, NUCB2 [odds ratio (OR) = 0.8634, 95% confidence interval (CI): 0.8145-0.9152, P < 0.0001], PGF (OR = 0.8393, 95% CI: 0.7185-0.9805, P < 0.05), and CRIM1 (OR = 0.7539, 95% CI: 0.6556-0.670, P < 0.0001), were identified as having a unidirectional causal association with PCOS and were associated with a reduced risk of PCOS. In public datasets, NUCB2 exhibited significantly increased expression in PCOS samples, while PGF and CRIM1 showed the opposite trends. These three genes were enriched in pathways related to cellular functions, metabolic processes, and the operation of the nervous system, and they were co-expressed in smooth muscle. Additionally, five cell clusters were annotated, among which fibroblasts were identified as key cells due to their highest expression of all three key genes. Further analysis revealed a bifurcation event occurring during the mid-development stage of fibroblasts, with PCOS samples displaying a higher abundance of fibroblasts. In PCOS samples, fibroblasts exhibited more extensive communication with secretory epithelial cells, indicating a more complex intercellular interaction within this condition. CONCLUSION This study identified three EMT-RGs: NUCB2, PGF, and CRIM1, which were associated with a reduced risk of PCOS, with fibroblast identified as a key cell group in the disease's pathology. This provides new insights for PCOS research.
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Affiliation(s)
- Dong Liu
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
| | - Dan Liu
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
- Department of Ultrasonic Medicine, West China Second University Hospital of Sichuan University, Chengdu, China
| | - Kunyan Zhou
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China.
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25
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Bernal JVM, da Veiga AC, Philbois SV, Ribeiro VB, Aguilar BA, Paixão TEV, Chinellato N, Sánchez-Delgado JC, Gastaldi AC, de Souza HCD. Women With Polycystic Ovary Syndrome and Excess Body Fat Exhibit Atypical Sympathetic Autonomic Modulation That is Partially Reversed by Aerobic Physical Training. Clin Endocrinol (Oxf) 2025; 102:178-189. [PMID: 39526386 DOI: 10.1111/cen.15163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 09/23/2024] [Accepted: 10/27/2024] [Indexed: 11/16/2024]
Abstract
OBJECTIVE The aetiology of impairments in autonomic modulation of heart rate variability (HRV) in polycystic ovary syndrome (PCOS) remains unclear, as does the impact of aerobic physical training (APT) on controlling endocrine-metabolic disorders and HRV. This is because these women often present excess body fat. Therefore, we assessed whether the dysregulation in autonomic modulation of HRV in women with PCOS is due to endocrine-metabolic disorders and whether the combination of excess body fat with endocrine-metabolic disorders amplifies cardiovascular autonomic deficits. We also investigated whether APT positively influences autonomic modulation of HRV in PCOS. DESIGN Non-randomised clinical trial. PARTICIPANTS Women with and without PCOS with different percentages of body fat. MEASUREMENTS Participants were divided into four groups: women without PCOS with a body fat percentage between 22% and 29% (CONTROL group; 22%-29%); CONTROL (30%-37%) group; PCOS (22%-29%) group; and PCOS (30%-37%) group. Hemodynamic, metabolic, and hormonal characteristics and HRV parameters were obtained before and after 16 weeks of APT. RESULTS The PCOS (22%-29%) group exhibited lower vagal modulation than the CONTROL (22%-29%) group. In contrast, no significant differences were observed between the CONTROL (30%-37%) and PCOS (30%-37%) groups. Furthermore, the PCOS (30%-37%) group demonstrated lower sympathetic modulation than the PCOS (22%-29%) group. After APT, the PCOS (22%-29%) group increased in vagal modulation, while the PCOS (30%-37%) group increased in sympathetic modulation. CONCLUSION PCOS affects vagal modulation; however, this effect may be masked at elevated levels of body fat. Additionally, the combination of excess body fat with endocrine-metabolic dysregulation appears to reduce sympathetic modulation, possibly due to sympathetic drive hyperactivity. APT positively affected HRV in both PCOS groups.
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Affiliation(s)
- João Vitor Martins Bernal
- Department of Health Sciences, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| | - Ana Catarine da Veiga
- Department of Health Sciences, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| | - Stella Vieira Philbois
- Department of Health Sciences, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| | - Victor Barbosa Ribeiro
- Department of Health Sciences, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| | - Bruno Augusto Aguilar
- Department of Health Sciences, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| | | | - Naiara Chinellato
- Department of Health Sciences, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| | | | - Ada Clarice Gastaldi
- Department of Health Sciences, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| | - Hugo Celso Dutra de Souza
- Department of Health Sciences, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
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Yadav S, Dadge S, Garg R, Goand UK, Agarwal A, Chauhan D, Gayen JR. Pancreastatin inhibitor PSTi8 improves ovarian health in Letrozole-HFD induced PCOS rats by ameliorating metabolic and reproductive parameters. Steroids 2025; 214:109558. [PMID: 39742935 DOI: 10.1016/j.steroids.2024.109558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 12/24/2024] [Accepted: 12/28/2024] [Indexed: 01/04/2025]
Abstract
Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder associated with insulin resistance (IR) and hyperandrogenism. IR plays a crucial role in the etiology of PCOS. An insulin-sensitizing agent like metformin is most commonly used as an off-label drug for the treatment of PCOS. PSTi8 (a pancreastatin inhibitor) is known as a promising therapeutic insulin-sensitizing agent for the treatment of IR in metabolic diseases. Thus, this study evaluates the insulin-sensitizing effects of PSTi8 compared to metformin on IR, hyperandrogenism, ovarian, and metabolic dysfunction in a PCOS model. To induce PCOS, rats were administered letrozole at a dose of 2 mg/kg via oral administration and fed a 60 % high-fat diet. Metformin and PSTi8 lowered serum insulin, testosterone, luteinizing hormone (LH) levels, and the LH/follicle-stimulating hormone ratio in the blood serum and improved steroidogenic gene expression in the PCOS ovaries. Both treatments increased the levels of sex hormone-binding globulin and estrogen hormone. Metformin and PSTi8 restore ovarian and uterine histomorphometry and improve the estrous cycle in PCOS rats. Metformin and PSTi8 treatments also improve blood glucose level and increase insulin sensitivity, inflammation, reactive oxygen species accumulation, lipid parameters, body weight, and fat mass in PCOS rats. This study revealed that PSTi8 is as helpful as metformin in decreasing hyperandrogenism by improving insulin sensitivity, free testosterone level and restoring disturbed reproductive and metabolic parameters in PCOS rats. PSTi8 has potential to serve as a therapeutic molecule for preventing IR induced by a western diet in PCOS.
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Affiliation(s)
- Shubhi Yadav
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow 226 031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziaba 201002, India
| | - Shailesh Dadge
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow 226 031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziaba 201002, India
| | - Richa Garg
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow 226 031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziaba 201002, India
| | - Umesh K Goand
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow 226 031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziaba 201002, India
| | - Arun Agarwal
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow 226 031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziaba 201002, India
| | - Divya Chauhan
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow 226 031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziaba 201002, India
| | - Jiaur R Gayen
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow 226 031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziaba 201002, India.
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Liu Z, Wang RH, Wang KH. Formononetin ameliorates polycystic ovary syndrome through suppressing NLRP3 inflammasome. Mol Med 2025; 31:27. [PMID: 39871124 PMCID: PMC11770978 DOI: 10.1186/s10020-025-01092-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Accepted: 01/17/2025] [Indexed: 01/29/2025] Open
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is a common gynecological disease accompanied by multiple clinical features, including anovulation, hyperandrogenism, and polycystic ovarian morphology, leading to infertility. Formononetin (FMN), which is a major bioactive isoflavone compound in Astragalus membranaceus, exerts anti-inflammatory effects. However, whether FMN is effective in the treatment of PCOS remains unknown. This study aims to explore the effects and the possible mechanisms of FMN in PCOS. METHODS Dehydroepiandrosterone (DHEA)-induced PCOS rats and dihydrotestosterone (DHT)-induced PCOS cell models were established. Fifty rats were randomly assigned into five groups of 10 rats each: Control, PCOS, PCOS + FMN (15 mg/kg), PCOS + FMN (30 mg/kg), and PCOS + FMN (60 mg/kg). Fasting blood glucose, insulin, luteinizing hormone, follicle-stimulating hormone, testosterone, and estradiol were detected in DHEA-induced PCOS rats. Ovarian histological changes and apoptosis were evaluated utilizing H&E and TUNEL staining. Subsequently, the effects of FMN on oxidative stress and inflammatory responses in the DHEA-induced PCOS rat model and DHT-induced PCOS cell model were explored. Besides, the function of FMN on cell viability and apoptosis in DHT-induced PCOS cell model were explored by using CCK-8 assay and flow cytometry. Protein expression was detected via western blot and immunofluorescence staining in the DHEA-induced PCOS rat model and DHT-induced PCOS cell model. RESULTS FMN alleviated PCOS symptoms and reduced inflammation, cell apoptosis, and oxidative stress in DHEA-induced PCOS rats and DHT-induced KGN cells. Additionally, FMN suppressed NLRP3 inflammasome activation in both models. In the DHT-induced PCOS cell model, nigericin (a activator of NLRP3) reversed the functions of FMN on inflammation, apoptosis, and oxidative stress. CONCLUSION These findings demonstrated that FMN could alleviate PCOS by repressing inflammation, apoptosis, as well as oxidative stress in vivo and in vitro via inhibition of the NLRP3 inflammasome. HIGHLIGHTS 1. FMN improved PCOS symptoms. 2. FMN alleviated cell apoptosis, inflammation and oxidative stress in PCOS. 3. FMN inhibited the activation of NLRP3 inflammasome in PCOS.
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Affiliation(s)
- Zhuo Liu
- Reproduction and Genetics Center, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 42 Wenhua West Road, Lixia District, Jinan, 250014, Shandong, China
| | - Rui-Han Wang
- The First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, China
| | - Ke-Hua Wang
- Reproduction and Genetics Center, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 42 Wenhua West Road, Lixia District, Jinan, 250014, Shandong, China.
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28
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Jin Q, Xu G, Ying Y, Liu L, Zheng H, Xu S, Yin P, Chen Y. Effects of non-pharmacological interventions on biochemical hyperandrogenism in women with polycystic ovary syndrome: a systematic review and network meta-analysis. J Ovarian Res 2025; 18:8. [PMID: 39833948 PMCID: PMC11744805 DOI: 10.1186/s13048-025-01595-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 01/08/2025] [Indexed: 01/22/2025] Open
Abstract
OBJECTIVE To systematically evaluate the effectiveness of non-pharmacological interventions (NPIs), including electroacupuncture, exercise, diet, and lifestyle changes, in reducing androgen levels in women with polycystic ovary syndrome (PCOS) through a systematic review and network meta-analysis. METHODS Comprehensive searches were conducted in PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wanfang up to June 2024. Randomized controlled trials (RCTs) comparing NPIs with other NPIs or placebo treatments in adult women with PCOS were included. Study selection was independently performed by three authors. Quality assessment followed PRISMA guidelines using the Cochrane RoB2 tool. The confidence of evidence was examined using Confidence in Network Meta-Analysis (CINeMA). Traditional meta-analysis of continuous variables was conducted using Stata 17.0 software with a random-effects model, reporting effect sizes as standardized mean differences (SMD) and weighted mean differences (WMD). Network meta-analysis (NMA) was used to synthesize data, with network diagrams illustrating comparisons between NPIs. We assessed the consistency of the results, performed sensitivity analyses, and examined publication bias to evaluate the influence of individual studies. Furthermore, subgroup analysis and network meta-regression analysis were conducted to explore potential sources of heterogeneity. RESULTS The review included 21 studies with 1,196 participants, with meta-analysis focusing on 17 studies involving 1,013 participants. NPIs significantly reduced serum testosterone (SMD = -0.57; 95% CI: -0.86 to -0.29, p < 0.01), A4 (SMD = -1.37; 95% CI: -2.63 to -0.12, p = 0.03), and mFG score (WMD = -0.81; 95% CI: -1.26 to -0.37, p < 0.01). Notably, the reduction in testosterone levels achieved with NPIs met the Minimum Clinically Important Difference (MCID) of 12.47 ng/dL (WMD = -12.57; 95% CI: -18.92 to -6.23; p < 0.01), affirming the clinical relevance of these reductions. No significant effects were observed on Free Androgen Index (FAI), Sex Hormone-Binding Globulin (SHBG), Dehydroepiandrosterone (DHEA), DHEA Sulfate (DHEAS), Free Testosterone (FT), or Dihydrotestosterone (DHT) levels (all p > 0.05). The NMA (18 studies, 1,067 participants) identified electroacupuncture combined with diet and exercise as the most effective intervention for reducing serum testosterone (WMD = -21.75; 95% CI: -49.58 to 6.07; SUCRA 72.3%). Evidence certainty for many interventions was low, highlighting the need for higher-quality studies. Sensitivity analysis confirmed the robustness of the findings, and no publication bias was detected. CONCLUSIONS NPIs, particularly electroacupuncture combined with exercise and dietary management, effectively reduce androgen levels in PCOS patients. These findings provide valuable guidance for clinicians and women with PCOS, with multi-component approaches recommended for more substantial clinical benefit. TRIAL REGISTRATION PROSPERO CRD42023426226.
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Affiliation(s)
- Qi Jin
- LongHua Hospital Shanghai University of Traditional Chinese Medicine, No.725 Wanping South Road, Xuhui District, Shanghai, 200032, China
- Shanghai Municipal Hospital of Traditional Chinese Medicine, China. No. 274 Zhijiang Middle Road, Jing'an District, Shanghai, 200071, China
| | - Ge Xu
- Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Pudong New Area, Shanghai, 201203, China
| | - Yuchen Ying
- LongHua Hospital Shanghai University of Traditional Chinese Medicine, No.725 Wanping South Road, Xuhui District, Shanghai, 200032, China
| | - Lumin Liu
- LongHua Hospital Shanghai University of Traditional Chinese Medicine, No.725 Wanping South Road, Xuhui District, Shanghai, 200032, China
| | - Huimin Zheng
- Shanghai Municipal Hospital of Traditional Chinese Medicine, China. No. 274 Zhijiang Middle Road, Jing'an District, Shanghai, 200071, China
| | - Shifen Xu
- Shanghai Municipal Hospital of Traditional Chinese Medicine, China. No. 274 Zhijiang Middle Road, Jing'an District, Shanghai, 200071, China
| | - Ping Yin
- LongHua Hospital Shanghai University of Traditional Chinese Medicine, No.725 Wanping South Road, Xuhui District, Shanghai, 200032, China.
| | - Yuelai Chen
- LongHua Hospital Shanghai University of Traditional Chinese Medicine, No.725 Wanping South Road, Xuhui District, Shanghai, 200032, China.
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Wu S, Wu Y, Fang L, Lu X. Association of insulin resistance surrogates with live birth outcomes in women with polycystic ovary syndrome undergoing in vitro fertilization. BMC Pregnancy Childbirth 2025; 25:25. [PMID: 39799297 PMCID: PMC11724488 DOI: 10.1186/s12884-024-07131-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 12/31/2024] [Indexed: 01/15/2025] Open
Abstract
BACKGROUND Insulin resistance (IR) is a common pathophysiologic feature in patients with polycystic ovary syndrome (PCOS). However, there have been no studies investigating the association of IR surrogates with pregnancy outcomes in women with PCOS undergoing in vitro fertilization (IVF). Therefore, we explored the association between these factors among PCOS patients. METHODS We conducted a retrospective study that included patients with PCOS who underwent IVF at a university-affiliated hospital. Blood samples and physical examinations are collected at reproductive center on fasting in the morning of the 2nd to 4th day of the menstrual cycle prior to medication. We categorized participants into "Non-IR group" (HOMA-IR < 2.2) and "IR group" (HOMA-IR ≥ 2.2). The association of IR surrogates [triglyceride-glucose-body mass index (TyG-BMI), triglyceride-glucose (TyG) and homeostasis model assessment (HOMA-IR)] with IVF outcomes was evaluated by regression model analysis. Moreover, we also performed sensitivity analyses with stratification and interaction tests. The primary outcome variable was the live birth rate. RESULTS A total of 543 PCOS patients were finally included in the study. In all three regression models for the fresh embryo transfer (ET) cycles, all three IR surrogates showed stable negative correlations with live birth rate (in Model III: TyG-BMI OR = 0.99, 95% CI: 0.98 ~ 0.99; TyG OR = 0.47, 95% CI: 0.27 ~ 0.82; HOMA-IR OR = 0.84, 95% CI: 0.72 ~ 0.97; all P < 0.05), and this association was stable across all subgroups of the population (all P-interaction > 0.05). However, this relationship did not exist in frozen-thawed embryo transfer (FET) cycles. Furthermore, our study found that TyG-BMI was superior to TyG and HOMA-IR in predicting the rate of live birth in fresh ET cycles [TyG-BMI: 0.64 (95% CI: 0.58, 0.69) vs. TyG: 0.61 (95% CI: 0.55, 0.67) vs. HOMA-IR: 0.60 (95% CI: 0.55, 0.67)]. CONCLUSIONS Our study revealed that the three IR surrogates (TyG-BMI, TyG and HOMA-IR) were negatively associated with the live birth rates in fresh ET cycles. However, this relationship did not exist in FET cycles. Furthermore, our study found that TyG-BMI was superior to TyG and HOMA-IR in predicting the rate of live birth in fresh ET cycles.
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Affiliation(s)
- Shenghao Wu
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
| | - Yanhong Wu
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
| | - Lizi Fang
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
| | - Xiaosheng Lu
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
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Allagui I, Sdayria J, Athmouni K, Zammel N, Guesmi F, Saoudi M, Giuffrè AM, Allagui MS, Nahdi S, Harrath AH. Cleome arabica L mitigates bisphenol A-induced ovarian dysfunction and inflammation in Wistar rats: biochemical, histopathological, pharmacokinetic, and in silico studies. 3 Biotech 2025; 15:21. [PMID: 39720094 PMCID: PMC11663833 DOI: 10.1007/s13205-024-04169-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 11/21/2024] [Indexed: 12/26/2024] Open
Abstract
The present study evaluated the antioxidant and anti-inflammatory properties of Cleome arabica (CA) fruit extract against bisphenol A (BPA)-induced ovarian injury in female Wistar rats. The antioxidant activity was estimated by the total antioxidant capacity (TAC) and superoxide radical (NBT) content. For the in vivo analyses, 24 animals were divided into the following 4 groups: the control group; the BPA group (50 mg/kg BW BPA for 30 days); the BPA + CA group (50 mg/kg BW BPA and 50 mg/kg BW CA); and the CA group (50 mg/kg BW CA). The in vitro results demonstrated that CA exhibited strong antioxidant activity and scavenged O2•- radicals. . Pharmacokinetic properties were also explored, reflecting the physiological dynamics of the five active molecules (quercetin, catechin, kaempferol, rosmarinic acid, and naringenin). The in vivo findings revealed a significant increase in body weight associated with a significant increase in plasma C-reactive protein (CRP), proinflammatory cytokines (IL-1, IL-6, and TNF-α), and testosterone levels (p < 0.01). In addition, ovarian histological disruption was observed. However, co-administration of CA extract significantly improved ovarian histological integrity and attenuated inflammatory and androgenic disturbances. Moreover, in silico investigations showed that CA compounds interacted more strongly with the active sites of IL-1β, IL-6, or TNF-α. The best binding energy was observed between catechin (five H-bonds) and IL-1β and IL-6, at -6.0 and -6.1 kcal/mol, respectively, and between rosmarinic acid (four H-bonds) and TNF-α, at -6.4 kcal/mol. The present study supports the use of Cleome arabica in the treatment of infertility for female polycystic ovary syndrome (PCOS) patients.
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Affiliation(s)
- Ikram Allagui
- Laboratory of Animal Ecophysiology, Faculty of Science, University of Sfax Tunisia, P.O. Box 95, CP 3000 Sfax, Tunisia
- Laboratory of Biotechnology and Biomonitoring of the Environment and Oasis Ecosystems, Faculty of Sciences of Gafsa, University Campus Sidi Ahmed Zarroug, University of Gafsa, 2112 Gafsa, Tunisia
| | - Jazia Sdayria
- Laboratory of Biotechnology and Biomonitoring of the Environment and Oasis Ecosystems, Faculty of Sciences of Gafsa, University Campus Sidi Ahmed Zarroug, University of Gafsa, 2112 Gafsa, Tunisia
| | - Khaled Athmouni
- Laboratory of Biodiversity and Aquatic Ecosystems, Ecology and Planctonology, Department of life sciences, Faculty of Sciences, University of Sfax Tunisia, Unit UR 11 ES 72/Street of Soukra Km 3,5, B.P. 1171, CP 3000 Sfax, Tunisia
| | - Nourhene Zammel
- Laboratory of Histo-Embryology and Cytogenetics, Medicine Faculty of Sfax, University of Sfax, 3029 Sfax, Tunisia
| | - Fatma Guesmi
- Laboratory of Biotechnology and Biomonitoring of the Environment and Oasis Ecosystems, Faculty of Sciences of Gafsa, University Campus Sidi Ahmed Zarroug, University of Gafsa, 2112 Gafsa, Tunisia
- Laboratory of Risks Related to Environmental Stresses: Fight and Prevention, Unit UR03ES06, Faculty of Sciences of Bizerte, University of Carthage, Carthage, Tunisia
| | - Mongi Saoudi
- Laboratory of Animal Ecophysiology, Faculty of Science, University of Sfax Tunisia, P.O. Box 95, CP 3000 Sfax, Tunisia
| | - Angelo Maria Giuffrè
- Department of AGRARIA, University Mediterranea of Reggio Calabria, 89124 Reggio Calabria, Italy
| | - Mohamed Salah Allagui
- Laboratory of Animal Ecophysiology, Faculty of Science, University of Sfax Tunisia, P.O. Box 95, CP 3000 Sfax, Tunisia
- Laboratory of Biotechnology and Biomonitoring of the Environment and Oasis Ecosystems, Faculty of Sciences of Gafsa, University Campus Sidi Ahmed Zarroug, University of Gafsa, 2112 Gafsa, Tunisia
| | - Saber Nahdi
- Department of Zoology, College of Science, King Saud University, 11451 Riyadh, Saudi Arabia
| | - Abdel Halim Harrath
- Department of Zoology, College of Science, King Saud University, 11451 Riyadh, Saudi Arabia
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Wang M, Huang J, Shi Y, Mprah R, Ding H, Zhang S, Li C. Exploring the efficacy of Wenshentiaojing decoction in PCOS: Network pharmacology and mouse model insights. Bioorg Chem 2025; 154:108089. [PMID: 39742672 DOI: 10.1016/j.bioorg.2024.108089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 12/11/2024] [Accepted: 12/21/2024] [Indexed: 01/04/2025]
Abstract
BACKGROUND Wenshentiaojing Decoction (WSTJD), a traditional Chinese herbal prescription, was first recorded in the "Ye Tianshi female department secret recipe for diagnosis and treatment ". It has been proven effective in treating polycystic ovary syndrome (PCOS). However, the active ingredients and molecular mechanism of WSTJD against PCOS remain unclear. AIM OF THE STUDY To explore the therapeutic effect and molecular mechanism of WSTJD against PCOS by using network pharmacology and mouse model. MATERIALS AND METHODS Network pharmacology were used to predict active ingredients, potential targets, and pathways of WSTJD against PCOS. Female mice were injected subcutaneously with DHEA (6 mg/100 g body weight) daily to establish a PCOS model and administered with WSTJD and quercetin to observe its therapeutic effect. Thereafter, mouse phenotypes, indicators related to oxidative stress and ferroptosis, and hub genes were determined. RESULTS We identified 144 potential targets for WSTJD in the treatment of PCOS, which were enriched in immune-related signaling pathways such as reactive oxygen species, TNF and IL-17 signaling pathway. Thirteen hub genes were identified by proteinprotein interaction network (PPI) and algorithmic analysis, all of which were oxidative stress-related genes, and five of which, IL6, PTGS2, HIF1A, MTOR and EGFR, were ferroptosis-related genes. Further analysis revealed that quercetin was a key ingredient for WSTJD and that it had superior binding effects with the hub genes. Moreover, WSTJD and quercetin could significantly depress oxidative stress-related indicators and ferroptosis-related gene expression in PCOS mice. Finally, mouse models showed that the expression of the hub genes were consistent with the analysis results. CONCLUSIONS WSTJD and quercetin alleviated PCOS by suppressing oxidative stress and ferroptosis. Quercetin was the key ingredient for WSTJD against PCOS.
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Affiliation(s)
- Mingming Wang
- Department of Physiology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, Jiangsu Province 221009, PR China; National Experimental Teaching Demonstration Center for Basic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu Province 221009, PR China.
| | - Jing Huang
- Department of Medical Informatics Engineering, Xuzhou Medical University, Xuzhou, Jiangsu Province 221009, PR China
| | - Yue Shi
- Department of Physiology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, Jiangsu Province 221009, PR China; National Experimental Teaching Demonstration Center for Basic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu Province 221009, PR China
| | - Richard Mprah
- Department of Physiology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, Jiangsu Province 221009, PR China
| | - Huanhuan Ding
- Department of Physiology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, Jiangsu Province 221009, PR China; National Experimental Teaching Demonstration Center for Basic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu Province 221009, PR China
| | - Shanshan Zhang
- School of Biological Science, Jining Medical University, Rizhao, Shandong Province 276826, PR China.
| | - Cui Li
- Department of Physiology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, Jiangsu Province 221009, PR China; National Experimental Teaching Demonstration Center for Basic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu Province 221009, PR China.
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Hu R, Huang Y, Liu Z, Dong H, Ma W, Song K, Xu X, Wu X, Geng Y, Li F, Zhang M, Song Y. Characteristics of polycystic ovary syndrome rat models induced by letrozole, testosterone propionate and high-fat diets. Reprod Biomed Online 2025; 50:104296. [PMID: 39626468 DOI: 10.1016/j.rbmo.2024.104296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 05/24/2024] [Accepted: 05/24/2024] [Indexed: 01/29/2025]
Abstract
RESEARCH QUESTION What are the long-term effects of different models of polycystic ovary syndrome (PCOS), and which model could be used in future research? DESIGN PCOS models induced by letrozole, letrozole plus high-fat diet (LE+HFD), testosterone propionate (TP) or testosterone propionate plus HFD (TP+HFD) were established in rats. Body weight, energy intake, blood glucose, sex hormone concentrations, lipid profiles and the oestrus cycle were observed. Histology of ovaries, large intestine and fat was displayed. Protein and mRNA levels relating to hormone synthesis, oocyte maturation, the gut barrier, lipid metabolism and inflammation were evaluated using western blotting, immunohistochemistry and PCR. The composition of the microbial community was measured using 16S RNA sequencing. RESULTS Letrozole treatment induced hyperandrogenaemia, polycystic ovarian morphology, a disrupted oestrus cycle and impaired ovarian function, which could be restored within 42 days. Concurrently, letrozole disturbed glucose, fat, and energy metabolism, affected the inflammatory state and compromised intestinal homeostasis. HFD could amplify the disturbances in the metabolism and intestinal microenvironment, and the pituitary-ovarian axis was more efficiently and consistently affected by testosterone propionate. Testosterone propionate and TP+HFD treatment also disturbed the intestinal microenvironment. Although the metabolic effects of testosterone propionate were not as profound as those of letrozole, they were enhanced by HFD. CONCLUSIONS Letrozole is useful for studies on metabolic disturbances in PCOS, and LE+HFD treatment is suitable for investigations on PCOS metabolic abnormalities and the gut-PCOS link. Testosterone propionate injection is appropriate for studying reproductive abnormalities in PCOS, while TP+HFD treatment is the most comprehensive for studying PCOS reproductive abnormalities, metabolic disturbances and the gut-PCOS link.
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Affiliation(s)
- Runan Hu
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yanjing Huang
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhuo Liu
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Haoxu Dong
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wenwen Ma
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Kunkun Song
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaohu Xu
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiao Wu
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yuli Geng
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fan Li
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Mingmin Zhang
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Yufan Song
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Wang M, Zhang S, He J, Zhang T, Zhu H, Sun R, Yang N. Biochemical classification diagnosis of polycystic ovary syndrome based on serum steroid hormones. J Steroid Biochem Mol Biol 2025; 245:106626. [PMID: 39448042 DOI: 10.1016/j.jsbmb.2024.106626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 08/31/2024] [Accepted: 10/21/2024] [Indexed: 10/26/2024]
Abstract
Polycystic ovary syndrome (PCOS) is a metabolic disorder with clinical heterogeneity. PCOS women with non-hyperandrogenemia (NA) might be misdiagnosed due to a lack of diagnostic markers. This study aims to systematically analyze the differences in steroid hormones between PCOS women with hyperandrogenemia (HA) and NA, and to screen classification diagnosis models for PCOS. The serum samples from 54 HA-PCOS, 79 NA-PCOS and 60 control women (Non-PCOS) aged between 18 and 35 were measured by an integrated steroid hormone-targeted quantification assay using LC-MS/MS. The levels of serum androgens, corticosteroids, progestins and estrogens in the steroid hormone biosynthesis pathway were analyzed in PCOS and Non-PCOS women. Eight machine learning methods including Linear Discriminant Analysis (LDA), K-nearest Neighbors (KNN), Boosted Logistic Regression (LogitBoost), Naive Bayes (NB), C5.0 algorithm (C5), Random Forest (RF), Support Vector Machines (SVM), and Neural Network (NNET) were performed, evaluated and selected for classification diagnosis of PCOS. A 10-fold cross-validation on the training set was performed. The whole metabolic flux from cholesterol to downstream steroid hormones increased significantly in PCOS, especially in HA-POCS women. The RF model was chosen for the classification diagnosis of HA-PCOS, NA-PCOS, and Non-PCOS women due to the maximum average accuracy (0.938, p<0.001), AUC (0.989, p<0.001), and kappa (0.906, p<0.001), and the minimum logLoss (0.200, p<0.001). Five steroid hormones including testosterone, androstenedione, total 2-methoxyestradiol, total 4-methoxyestradiol, and free estrone were selected as the decision trees for the simplified RF model. A total of 37 women were included in the validation set. The diagnostic sensitivity for HA-PCOS, NA-PCOS, and Non-PCOS was 100 %, 93.3 % and 91.7 %, respectively. HA-PCOS, NA-PCOS, and Non-PCOS women showed obvious different steroid hormone profiles. The simplified RF model based on two androgens and three estrogens could be effectively applied to the classification diagnosis of PCOS, further reducing the missed diagnosis rate of NA-PCOS.
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Affiliation(s)
- Min Wang
- Department of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China
| | - Shuhan Zhang
- Department of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China; Department of Pharmacy, China Pharmaceutical University Nanjing Drum Tower Hospital, Nanjing, Jiangsu 210000, China
| | - Jun He
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Tianqi Zhang
- Department of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China
| | - Huaijun Zhu
- Department of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China
| | - Runbin Sun
- Phase I Clinical Trials Unit, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.
| | - Na Yang
- Department of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China.
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Butler AE, Nandakumar M, Sathyapalan T, Brennan E, Atkin SL. Matrix Metalloproteinases, Tissue Inhibitors of Metalloproteinases, and Their Ratios in Women with Polycystic Ovary Syndrome and Healthy Controls. Int J Mol Sci 2025; 26:321. [PMID: 39796177 PMCID: PMC11720512 DOI: 10.3390/ijms26010321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 12/23/2024] [Accepted: 12/30/2024] [Indexed: 01/13/2025] Open
Abstract
Matrix metalloproteinases (MMPs) are M2 macrophage markers that are modulated by inflammation. A disintegrin and metalloproteinases (ADAMS) and those with thrombospondin motifs (ADAMTS) regulate the shedding of membrane-bound proteins, growth factors, cytokines, ligands, and receptors; MMPs, ADAMS, and ADAMTS may be regulated by tissue inhibitors of metalloproteinases (TIMPs). This study aimed to determine whether these interacting proteins were dysregulated in PCOS. A Somascan proteomic analysis of 12 MMPs, three of their inhibitors (TIMP-1, 2, 3), two ADAMS (9, 12), five ADAMTS (1, 4, 5, 13, 15), insulin-like growth factor binding protein-1 (IGFBP-1), and insulin-like growth factor-1 (IGF-1) was undertaken in a well-validated PCOS database of 143 women with PCOS and 97 controls. Women with PCOS had significantly higher levels of MMP-9 and lower levels of MMP-2, MMP-14, TIMP-2, IGFBP-1, and IGF-1 compared to the controls (p < 0.0001, p < 0.005, p < 0.04, p < 0.05, p < 0.0001, and p < 0.0001, respectively). No differences were observed for any other MMPs. The ADAMS or ADAMTS levels did not differ between groups. Body mass index (BMI) was correlated with MMP-9 (p < 0.01), MMP-1 (p < 0.05), MMP-2 (p < 0.05), MMP-10 (p < 0.005), MMP-12 (p < 0.005), ADAM-9 (p < 0.05), and IGFBP-1 (p < 0.0001), but only MMP-9 still differed after accounting for BMI. MMP-9/TIMP-1, MMP-9/TIMP-2, and MMP-9/TIMP-3 ratios were higher in the PCOS group (p < 0.01), whilst MMP-17/TIMP-1 and MMP-17/TIMP-2 were lower (p = 0.01). MMP-2/TIMP ratios showed no difference between groups. TIMP-2 was positively correlated with CRP (p < 0.01). MMP changes in PCOS are largely driven by BMI, though increased MMP-9 is BMI-independent, suggesting that any deleterious effects of MMP-9 would be potentially exacerbated by a concomitantly increased BMI. The significant increases in the MMP-9/TIMP ratios suggests MMP-9 overactivity in PCOS.
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Affiliation(s)
- Alexandra E. Butler
- Research Department, Royal College of Surgeons of Ireland, Adliya 15503, Bahrain; (M.N.); (E.B.); (S.L.A.)
| | - Manjula Nandakumar
- Research Department, Royal College of Surgeons of Ireland, Adliya 15503, Bahrain; (M.N.); (E.B.); (S.L.A.)
| | - Thozhukat Sathyapalan
- Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull HU6 7RX, UK;
| | - Edwina Brennan
- Research Department, Royal College of Surgeons of Ireland, Adliya 15503, Bahrain; (M.N.); (E.B.); (S.L.A.)
| | - Stephen L. Atkin
- Research Department, Royal College of Surgeons of Ireland, Adliya 15503, Bahrain; (M.N.); (E.B.); (S.L.A.)
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Li J, Zheng R, Shen Y, Zhuo Y, Lu L, Song J, Li J, Lai M, Zhu H, Hu M, Ma H, Li J. Jiawei Qi Gong Wan improves liver fibrosis and inflammation in PCOS mice via the Akt2-FoxO1 and YAP/TAZ signaling pathways. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2025; 136:156294. [PMID: 39616732 DOI: 10.1016/j.phymed.2024.156294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Revised: 11/19/2024] [Accepted: 11/23/2024] [Indexed: 01/16/2025]
Abstract
BACKGROUND Metabolic disorders in polycystic ovary syndrome (PCOS) patients have attracted increasing attention, and nonalcoholic fatty liver disease (NAFLD) in particular has been the focus of much research due to its high incidence and potential harm in patients with PCOS. However, little is known about whether PCOS is associated with more severe NAFLD histopathology. Although Jiawei Qi Gong Wan (JQGW) is widely used clinically, its specific effects and mechanisms on the liver remain unclear. PURPOSE The aim of this study was to explore the mechanism of JQGW in improving metabolic abnormalities in the liver in PCOS mice in order to support the development of therapies to prevent PCOS complications. METHODS A mouse model of PCOS was established by subcutaneously implanting letrozole tubes. The effect of JQGW on liver metabolism in mice was observed by measuring biochemical indicators in serum. Liver morphological changes were observed using hematoxylin and eosin staining along with Sirius red staining, while Western blotting and qRT-PCR were used to quantify the expression of genes and proteins related to liver fibrosis and inflammation processes. Network pharmacology was used to analyze the key factors that JQGW may target in improving liver fibrosis in PCOS mice, and the results were verified by Western blotting of liver tissue from PCOS mice. RESULTS PCOS mice had obvious liver metabolic dysfunction, inflammation, and fibrosis, all of which could be reversed by JQGW. Network pharmacology functional enrichment revealed that the overlapping targeted genes were enriched mainly in insulin resistance-related pathways and androgen-related pathways. We verified related proteins and found that JQGW improved liver fibrosis and inflammation in PCOS mice mainly by regulating the Akt2-FoxO1 and YAP/TAZ signaling pathways. CONCLUSION JQGW can improve liver metabolic function in a letrozole-induced PCOS mouse model by inhibiting liver fibrosis and inflammation, and it acts mechanistically by regulating the Akt2-FoxO1 and YAP/TAZ signaling pathways. Our findings thus provide a valuable reference for the advancement of therapeutic strategies aimed at addressing PCOS patients with abnormal liver metabolism.
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Affiliation(s)
- Jie Li
- Department of Traditional Chinese Medicine, The Key Laboratory of Advanced Interdisciplinary Studies, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China
| | - Ruqun Zheng
- Department of Traditional Chinese Medicine, The Key Laboratory of Advanced Interdisciplinary Studies, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China; Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Yingyan Shen
- Department of Traditional Chinese Medicine, The Key Laboratory of Advanced Interdisciplinary Studies, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China
| | - Yuxuan Zhuo
- Department of Traditional Chinese Medicine, The Key Laboratory of Advanced Interdisciplinary Studies, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China
| | - Lingjing Lu
- Department of Traditional Chinese Medicine, The Key Laboratory of Advanced Interdisciplinary Studies, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China; Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Jinlong Song
- Department of Laboratory Medicine, The Key Laboratory of Advanced Interdisciplinary Studies, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Jing Li
- State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
| | - Maohua Lai
- Department of Traditional Chinese Medicine, The Key Laboratory of Advanced Interdisciplinary Studies, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China
| | - He Zhu
- School of Public Health, Peking University, Beijing, China
| | - Min Hu
- Department of Traditional Chinese Medicine, The Key Laboratory of Advanced Interdisciplinary Studies, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China
| | - Hongxia Ma
- Department of Traditional Chinese Medicine, The Key Laboratory of Advanced Interdisciplinary Studies, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China.
| | - Juan Li
- Department of Traditional Chinese Medicine, The Key Laboratory of Advanced Interdisciplinary Studies, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China.
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Mrabet HE, Ben Salem H, Ach T, Ben Abdelkarim A, Alaya W. Effects of SGLT-2 inhibitors on clinical and biological hyperandrogenism and menstruation irregularities in patients with polycystic ovary syndrome: A systematic review of randomized trials. SAGE Open Med 2024; 12:20503121241308997. [PMID: 39713268 PMCID: PMC11660270 DOI: 10.1177/20503121241308997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Accepted: 12/05/2024] [Indexed: 12/24/2024] Open
Abstract
Introduction Polycystic ovary syndrome is a common chronic condition characterized by insulin resistance and hyperandrogenism, leading to significant health risks and impaired quality of life. Sodium-glucose transporter type 2 inhibitors have shown promise in improving the metabolic profile of women with polycystic ovary syndrome. However, their impact on hormonal parameters and cycle disorders remains uncertain. Methods This systematic review analyzed randomized clinical trials published up to 1 December 2023, comparing sodium-glucose transporter type 2 inhibitors to metformin, other antidiabetic agents, or placebo in women with polycystic ovary syndrome. The primary outcomes were changes in total testosterone, free androgen index, dehydroepiandrosterone sulfate, delta-4 androstenedione, and cycle disorders. Results Five randomized studies were included, evaluating canagliflozin, dapagliflozin, licogliflozin, or empagliflozin against metformin, exenatide, or placebo, with a total of 214 participants. Improvements in total testosterone and dehydroepiandrosterone sulfatewere observed in some studies, but the effects were inconsistent across drugs and outcomes. Additionally, two studies reported beneficial effects on cycle disorders. Conclusions Sodium-glucose transporter type 2 inhibitors appear to have a potential but variable impact on hormonal parameters in women with polycystic ovary syndrome. However, larger and longer-duration studies are needed to fully elucidate their long-term efficacy in addressing hyperandrogenism and improving overall outcomes in these patients.
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Affiliation(s)
- Houcem Elomma Mrabet
- Department of Endocrinology, Diabetology, and Internal Medicine, Tahar Sfar University Hospital, Mahdia, Tunisia
| | - Houda Ben Salem
- Department of General Medicine, Eljem Constituency Hospital, Eljem, Mahdia, Tunisia
| | - Taieb Ach
- Department of Endocrinology, Farhat Hachad University Hospital, Sousse, Tunisia
| | - Asma Ben Abdelkarim
- Department of Endocrinology, Farhat Hachad University Hospital, Sousse, Tunisia
| | - Wafa Alaya
- Department of Endocrinology, Diabetology, and Internal Medicine, Tahar Sfar University Hospital, Mahdia, Tunisia
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Zhu M, Wang K, Feng J, Liu Y, Guan M, Wang Y, Wu X. The waist-to-height ratio is a good predictor for insulin resistance in women with polycystic ovary syndrome. Front Endocrinol (Lausanne) 2024; 15:1502321. [PMID: 39717101 PMCID: PMC11664359 DOI: 10.3389/fendo.2024.1502321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 11/18/2024] [Indexed: 12/25/2024] Open
Abstract
Objective This study aimed to explore the role of the waist-to-height ratio (WHtR) in assessing insulin resistance (IR) in patients with polycystic ovary syndrome (PCOS). Materials and methods We enrolled 882 PCOS-afflicted women in a cross-sectional analysis to evaluate the association of the WHtR with IR. Their demographic characteristics, anthropometric parameters, and fasting blood samples were collected and measured. Moreover, IR was evaluated by homeostatic model assessment of insulin resistance (HOMA-IR). We estimated the relationship between the WHtR and IR and the cut-off thresholds of the WHtR for IR using multivariable linear regression and logistic regression models, respectively. Results The prevalence rate of IR was 51.9%. The patients with PCOS and IR displayed significantly increased values for body mass index (BMI), waist circumference (WC), WHtR, systolic blood pressure (SBP), diastolic blood pressure (DBP), free androgen index (FAI), HOMA-IR, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (ApoB). However, the patients with PCOS and IR showed a reduction in estradiol (E2), luteinizing hormone (LH), LH/FSH ratio, sex hormone binding globulin (SHBG), and high-density lipoprotein (HDL-C) values than those without IR. Moreover, BMI (log-transformed), WC, and HOMA-IR (log-transformed) were positively correlated with the WHtR. When adjusting for potential confounding variables, the WHtR was significantly associated with HOMA-IR (log-transformed), with a standardized regression coefficient of 0.271. Furthermore, the WHtR was significantly associated with an increased risk of IR, with the adjusted odds ratio (OR) of 3.15 (WHtR multiplied by 10). Additionally, the WHtR helped to identify IR in women with PCOS with an optimal cut-off point of 0.519 (Youden index = 0.433). Conclusions The WHtR had a positive association with IR in women with PCOS. Hence, we suggest that the WHtR, as a simple, practical, and reliable anthropometric measure, can be used to predict the risk of IR in patients with PCOS.
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Affiliation(s)
- Mengyi Zhu
- Graduate School, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Kaiyue Wang
- Graduate School, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Jiaxing Feng
- First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Yang Liu
- First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Muxin Guan
- Graduate School, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Yu Wang
- First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Xiaoke Wu
- First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
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Tafazoli P, Rad HM, Mashayekhi M, Siadat SF, Fathi R. miRNAs in ovarian disorders: Small but strong cast. Pathol Res Pract 2024; 264:155709. [PMID: 39522318 DOI: 10.1016/j.prp.2024.155709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 11/01/2024] [Accepted: 11/05/2024] [Indexed: 11/16/2024]
Abstract
PURPOSE This research aimed to analyze alterations in microRNA expression in the diseases POF (Premature Ovarian Failure), PCOS (Polycystic Ovarian Syndrome), and ovarian cancer in order to understand the molecular changes associated with these conditions. The findings could potentially be utilized for diagnostic, therapeutic, predictive, and preventive purposes. Furthermore, the impact and role of microRNAs in each ailment, along with their functional pathways, were elucidated and examined. METHODS In this study, the genes involved in the disease were studied, and then the miRNAs that targeted these genes were evaluated, and finally the signaling and functional pathways of each of the miRNAs were assessed. In this process, genetic databases and previous studies were carefully assessed. RESULTS miRNAs are short nucleotide sequences that belong to the category of non-coding RNAs. They play a crucial role in various physiological activities, including cell division, growth, differentiation, and cell death (necrosis and apoptosis), miRNAs are involved in various physiological processes Such alterations are common in various diseases, including cancer. miRNAs are involved in various physiological processes, such as folliculogenesis and steroidogenesis, as well as in pathological conditions such as POF, PCOS, and ovarian cancer. They have powerful regulatory effects and controlling the most activities of normal and pathological cells. While microRNAs (miRNAs) play a significant role in normal ovarian functions, there are reports of their expression changes in PCOS, ovarian cancer, and POF. CONCLUSIONS miRNAs have been found to exert significant influence on both physiological and pathological cellular processes. Understanding the dynamic patterns of miRNA alterations can provide valuable insights for researchers and therapists, enabling them to utilize these biomarkers effectively in diagnostic, therapeutic, and preventive applications.
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Affiliation(s)
- Parsa Tafazoli
- Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Hanieh Motahari Rad
- Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
| | - Mehri Mashayekhi
- Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | | | - Rouhollah Fathi
- Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
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Hofmann K, Oehler M, Ruckes C, Dionysopoulou A, Stewen K, Schiestl LJ, Degirmenci Y, Theis S, Skala C, Hasenburg A, Schwab R. Gaps in knowledge regarding the diagnostic criteria and management of PCOS in Germany: An anonymous web-based survey. Heliyon 2024; 10:e40431. [PMID: 39641034 PMCID: PMC11617859 DOI: 10.1016/j.heliyon.2024.e40431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 10/30/2024] [Accepted: 11/13/2024] [Indexed: 12/07/2024] Open
Abstract
Introduction Polycystic Ovary Syndrome (PCOS) is a multifactorial condition that can include a myriad of symptom complexes. A study in North America demonstrated that a significant percentage of physicians were unaware of crucial aspects of PCOS. This study aimed to examine the level of knowledge about PCOS among physicians in Germany. Methods An anonymous cross-sectional online questionnaire was distributed to all gynecological clinics and fertility centers in Germany. The responsible gynecologists in service were contacted and they were asked to distribute the questionnaire among the employed physicians in their clinic. Results and discussion The questionnaire was completed 206 times. 92 (65.7 %) of all respondents were board-certified gynecologists without specialty training in reproductive medicine and gynecologic endocrinology (Non-RMGE), 48 (34.3 %) had completed this training (RMGE). RMGE were more likely to know the correct criteria for the diagnosis of PCOS (97.9 % vs. 51.3 %; p < 0.001) and were able to name a higher number of correct symptoms that may be associated with PCOS (20.8 vs. 14.0; p < 0.001) than Non-RMGE (B = 4.530, CI 1.379-7.680; p = 0.006). The preferred general treatments and fertility treatments for PCOS patients also differed significantly between the two groups (p = 0.002, p < 0.001). The participants were asked how doctors and healthcare professionals could be best supported to improve the care of PCOS patients. Over 58.3 % of participants considered the creation of a PCOS website dedicated to healthcare professionals to be valuable. Conclusion This study is the first to identify knowledge gaps about PCOS among physicians in Germany. The findings also highlight the potential disparities in PCOS knowledge between hospital and fertility center settings, emphasizing the need for improved training to ensure consistent and high-quality care for PCOS patients. The participants preferred a dedicated website for health professionals, indicating a demand for easily accessible information and training resources.
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Affiliation(s)
- Konstantin Hofmann
- Department of Obstetrics and Gynecology, University Medical Center of Johannes Gutenberg University Mainz, Germany
| | - Melody Oehler
- University Medical Center of Johannes Gutenberg University Mainz, Germany
| | - Christian Ruckes
- Institute of Medical Biostatistics, Epidemiology, and Informatics, University Medical Center of Johannes Gutenberg University Mainz, Germany
| | - Anna Dionysopoulou
- Department of Obstetrics and Gynecology, University Medical Center of Johannes Gutenberg University Mainz, Germany
| | - Kathrin Stewen
- Department of Obstetrics and Gynecology, University Medical Center of Johannes Gutenberg University Mainz, Germany
| | - Lina Judit Schiestl
- Department of Obstetrics and Gynecology, University Medical Center of Johannes Gutenberg University Mainz, Germany
| | - Yaman Degirmenci
- Department of Obstetrics and Gynecology, University Medical Center of Johannes Gutenberg University Mainz, Germany
| | - Susanne Theis
- Department of Obstetrics and Gynecology, University Medical Center of Johannes Gutenberg University Mainz, Germany
| | - Christine Skala
- Department of Obstetrics and Gynecology, University Medical Center of Johannes Gutenberg University Mainz, Germany
| | - Annette Hasenburg
- Department of Obstetrics and Gynecology, University Medical Center of Johannes Gutenberg University Mainz, Germany
| | - Roxana Schwab
- Department of Obstetrics and Gynecology, University Medical Center of Johannes Gutenberg University Mainz, Germany
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Ren M, Yang T, Liu M, Ma X, Li B, Al-Mughalles AS, Pei X, Zhang S. Application of small animal ultrasound imaging technology for identification of polycystic ovary syndrome in a mouse model. Biochem Biophys Res Commun 2024; 733:150634. [PMID: 39307110 DOI: 10.1016/j.bbrc.2024.150634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 08/14/2024] [Accepted: 08/29/2024] [Indexed: 10/06/2024]
Abstract
BACKGROUND AND AIMS Polycystic ovary syndrome (PCOS) is a hormonal disorder common among women of reproductive age, characterized by irregular menstrual periods, elevated levels of androgens, and polycystic ovaries, leading to various symptoms and complications such as infertility, metabolic issues, and increased risk of diabetes and heart disease. This study aimed to compare traditional histological methods and ultrasound imaging for consistency in identifying PCOS in a mouse model. The shortest time to construct the PCOS model using letrozole was determined. METHODS Female C57/BL mice were randomly divided into three groups: Group A received normal saline and a regular diet; Group B received 1 mg/kg/day of letrozole with a regular diet; and Group C received 1 mg/kg/day of letrozole with a high-fat diet. All mice were administered letrozole by intragastric gavage daily for five weeks. The traditional identification method included measuring body weight, examining vaginal smears, monitoring the estrous cycle, measuring serum androgen levels, and performing H&E staining of ovarian tissues. The PCOS model was evaluated using ultrasound imaging to identify and monitor follicles. The significance of the difference between the traditional identification method and the ultrasonic method was calculated using the nonparametric McNemar test, and consistency between the two methods was assessed with the kappa-coefficient test. On this basis, the ultrasound imaging technology was used to monitor the model-making process for 2, 3 and 4 weeks, and to monitor the parameters of the ovary and follicles to judge the shortest time that gavage letrozole caused the appearance of vesicular follicles in the mouse ovary. RESULTS The traditional identification method showed no PCOS phenotype in group A mice, while groups B and C showed multiple ovarian cystic follicles, indicating successful model induction. The ultrasound imaging results were consistent with the traditional method, showing no PCOS in group A and multiple cystic follicles in groups B and C. The McNemar test revealed no significant difference between the traditional and ultrasonic identification methods. The kappa-coefficient test assessed consistency, yielding a value of 0.903, indicating strong agreement between the methods. The ovarian area, diameter, and the number and diameter of cystic follicles were not significantly changed at two weeks in the letrozole group compared with the control group. At three weeks, there were significant increases in the number and in the diameter of vesicular follicles compared with control cells. At four weeks, the number and diameter, the maximum cross-sectional area and diameter of the ovary were significantly increased compared with the control group. CONCLUSIONS The ultrasound and traditional methods provide consistent results for identifying PCOS in a mouse model. Construction of the PCOS model by letrozole gavage takes at least three weeks.
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Affiliation(s)
- Mengmeng Ren
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, China; Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, 750004, China; Yinchuan Maternal and Child Health Care Hospital, Yinchuan, 750004, China
| | - Tingting Yang
- Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, 750004, China
| | - Meichen Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, China
| | - Xiaojuan Ma
- Department of Ultrasound Medicine, Ningxia Hui Autonomous Region People's Hospital, Yinchuan, 750004, China
| | - Boya Li
- Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, 750004, China
| | - Akram S Al-Mughalles
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, China
| | - Xiuying Pei
- Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, 750004, China
| | - Shuya Zhang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, China; Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, 750004, China.
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Li M, Zhang L, Li X, Yan W. Association between estimated glucose disposal rate and female infertility: a cross-sectional study. Front Endocrinol (Lausanne) 2024; 15:1474738. [PMID: 39600947 PMCID: PMC11588443 DOI: 10.3389/fendo.2024.1474738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Accepted: 10/21/2024] [Indexed: 11/29/2024] Open
Abstract
Background Insulin resistance (IR) can lead to infertility in women. The primary objective of this research was to examine how estimated glucose disposal rate (eGDR) correlates with infertility in women, assessing its validity as an indicator of IR. Methods Data from the National Health and Nutrition Examination Survey spanning 2013 to 2018 were analyzed in this study. In order to investigate the correlation between eGDR and the prevalence of female infertility, this study used a combination of weighted multivariate regression analysis, restricted cubic spline (RCS) analysis, subgroup analyses, sensitive analysis, and receiver operating characteristic (ROC) curves. Results This study enrolled 2541 women, with an average age of (32.52 ± 0.23) years. The overall infertility rate was 14.27%. A negative relationship was observed between eGDR levels and female infertility. Each increment of one unit in eGDR was linked to a 14% reduction in infertility incidence (OR = 0.86, 95% CI 0.80-0.94). RCS analysis revealed a nonlinear, inverse correlation between eGDR and female infertility. Subgroup analyses indicated that age influenced the association between eGDR and female infertility. The ROC curve suggested that eGDR was significantly better than HOMA-IR in predicting infertility [eGDR: 0.632 (95% CI: 0.603, 0.660) vs. HOMA-IR: 0.543 (95% CI: 0.514, 0.572)]. Conclusion There was an observed association where lower eGDR levels were linked with higher rates of female infertility. These results emphasize the significance of implementing measures to manage IR to protect women's reproductive health.
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Affiliation(s)
- Meng Li
- Department of Gynecology, Fuxing Hospital, Capital Medical University, Beijing, China
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Liu F, Tian L, Zhang Y, Deng W, Xu X, Zou Y, An R. DIA proteomic and PRM validation through human granulose cells profiles screen suitable biomarkers for polycystic ovary syndrome patients. J Proteomics 2024; 309:105332. [PMID: 39424224 DOI: 10.1016/j.jprot.2024.105332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 10/12/2024] [Accepted: 10/12/2024] [Indexed: 10/21/2024]
Abstract
The aim of this study is to identify differentially expressed proteins (DEPs) in granulose cells (GCs) from women with or withoutpolycystic ovary syndrome (PCOS) via data independent acquisition (DIA) proteomic analysis.A total of 63 women were recruited for this study, 34 PCOS patients as experimental group (P), and 29 women without PCOS as Normal group (NP). DIA-based proteomic analysis was performed to identify DEPs in GCs between the P and NP samples. Certain typical DEPs were further validated by Parallel reaction monitoring (PRM), and correlation analysis was performed between these DEPs and the clinical characteristics.Cell vitality was measured by CCK-8 assay. DIA analysis revealed 174 significantly DEPs, of which 7 were upregulated and 167 downregulated. Bioinformatics analysis was performed to analysis the significantly DEPs. The PRM experiment confirmed TOP2A and SPHKAP were upregulated significantly in P by comparing to NP, while GM2A, MRPS16, APOA2 and FGF2 were downregulated significantly. Most notably, Correlation analysis revealed that TOP2A, SPHKAP, MRPS16 and FGF2were positively correlated with TG, AMH and Age, but negatively correlated with Menarche age, DBIL, FT3, Basal serum FSH and LH.Meanwhile, CCK-8 assay has shown that downregulation of FGF2 could weaken cell viability. Finally, a panel of DEPs were identified in the GCs of patients with PCOS, of which certain significant DEPs might play essential roles in the pathogenesis of PCOS, could be regarded as candidate biomarkers for PCOS.
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Affiliation(s)
- Faying Liu
- Department of Obstetrics and Gynecology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Central Laboratory, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China; Jiangxi Key Laboratory of Reproductive Health, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China
| | - Lifeng Tian
- Reproductive Medicine Center, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China
| | - Ying Zhang
- Central Laboratory, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China
| | - Wei Deng
- Department of Obstetrics and Gynecology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang 321099, China
| | - Xiaoyun Xu
- Department of Quality Control, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China
| | - Yang Zou
- Central Laboratory, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China; Jiangxi Key Laboratory of Reproductive Health, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China
| | - Ruifang An
- Department of Obstetrics and Gynecology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
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Ling S, Huang L, Lia T, Xie D, Qin X, Tian C, Qin L. Identification and validation of core genes associated with polycystic ovary syndrome and metabolic syndrome. Medicine (Baltimore) 2024; 103:e40162. [PMID: 39432623 PMCID: PMC11495751 DOI: 10.1097/md.0000000000040162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 10/02/2024] [Indexed: 10/23/2024] Open
Abstract
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting women of reproductive age, affecting reproductive health, and increasing the incidence of diabetes mellitus and hypertension. Metabolic syndrome (MetS) is the most common metabolic disorder. Although clinical studies have shown a close association between PCOS and MetS, the molecular mechanisms are unknown. In this study, datasets of PCOS and MetS were obtained from the Gene Expression Omnibus database; differential expression analysis and weighted gene coexpression network analysis (WGCNA) were performed; and gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses also performed of differentially expressed genes (DEGs). The PCOS- and MetS-coexpressed DEGs were subsequently intersected with the coexpressed genes in the WGCNA module to obtain the core genes. By constructing receiver operating characteristic curves, we verified the predictive effects of the core genes. We also validated the expression of the core genes in the datasets. Finally, we verified the expression of the core genes by quantitative polymerase chain reaction in human follicular fluid granulosa cells. In addition, we used Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts to analyze the immune infiltration of immune cells in PCOS and MetS. Finally, we obtained 52 coexpressed DEGs of PCOS and MetS and 3 coexpressed genes in the WGCNA module. By taking the intersection of coexpressed DEGs and coexpressed genes of the WGCNA module, we get ELOVL fatty acid elongase 7 (ELOVL7) as the core gene. Receiver operating characteristic curve analysis showed that ELOVL7 is a reliable biological marker for PCOS and MetS. The expression level of ELOVL7 in human follicular fluid granulosa cells from PCOS patients was significantly higher than that of controls, as verified by quantitative polymerase chain reaction. This study provides the first evidence of the role of ELOVL7 in developing PCOS and MetS. This gene may serve as a potential diagnostic marker and therapeutic target for both conditions.
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Affiliation(s)
- Shaohua Ling
- Reproductive Medicine Center, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
- Reproductive Medicine Center, The Southwest Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
| | - Liying Huang
- Reproductive Medicine Center, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
| | - Thongher Lia
- Department of Urology Surgery, Chengdu Second People’s Hospital, Chengdu, China
| | - Delong Xie
- Reproductive Medicine Center, The Southwest Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
| | - Xiao Qin
- Reproductive Medicine Center, The Southwest Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
| | - Chun Tian
- Reproductive Medicine Center, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
| | - Li Qin
- Reproductive Medicine Center, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
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Luo M, Yang X, Zhou M, Zhang J, Yu B, Lian H, Ye J. Integrated single-cell and spatial transcriptomics reveal microenvironment disruptions by androgen in mouse ovary. iScience 2024; 27:111028. [PMID: 39429789 PMCID: PMC11490719 DOI: 10.1016/j.isci.2024.111028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 08/26/2024] [Accepted: 09/20/2024] [Indexed: 10/22/2024] Open
Abstract
Elevated levels of androgen are risk factors for disrupted follicular maturation in the polycystic ovary syndrome (PCOS), a reproductive disease in women. As essential cell types for follicular maturation, granulosa and thecal cells respond to androgen, but their responses are unclear at the subpopulation level. Using single-cell RNA sequencing and spatial transcriptomics, we examined the subpopulation and function alterations in an androgen-induced PCOS-like mouse model. The results demonstrated that the granulosa cell subset 5 (GC5) was active in inflammation and the thecal cell subtype 2 (TC2) had an enhanced activity in lipid metabolism. The two subsets were expanded in population size and intercellular signaling pathways, such as Ptn-Ncl and Mdk-Ncl. The results reveal that androgen induced landscape and function shifts in the two cell types under the condition of impaired follicular maturation. The study characterizes the ovarian microenvironment in responses to androgen in PCOS mice.
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Affiliation(s)
- Man Luo
- Institute of Trauma and Metabolism, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China
- School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
- Department of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China
| | - Xiaofeng Yang
- Department of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China
| | - Mengsi Zhou
- Department of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China
| | - Jing Zhang
- Science Island Branch of Graduate School, University of Science and Technology of China, Hefei 230036, China
| | - Biao Yu
- Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
- NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei 230032, China
| | - Hongkai Lian
- Institute of Trauma and Metabolism, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China
| | - Jianping Ye
- Institute of Trauma and Metabolism, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China
- School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
- Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, China
- Zhengzhou Key Laboratory for Obesity Research, Zhengzhou 450007, China
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Wang J, Huang Z, Cao Z, Luo Y, Liu Y, Cao H, Tang X, Fang G. Loureirin B Reduces Insulin Resistance and Chronic Inflammation in a Rat Model of Polycystic Ovary Syndrome by Upregulating GPR120 and Activating the LKB1/AMPK Signaling Pathway. Int J Mol Sci 2024; 25:11146. [PMID: 39456928 PMCID: PMC11508921 DOI: 10.3390/ijms252011146] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 10/07/2024] [Accepted: 10/12/2024] [Indexed: 10/28/2024] Open
Abstract
Polycystic ovary yndrome (PCOS) is a common metabolic disorder in women, which is usually associated with insulin resistance (IR) and chronic inflammation. Loureirin B (LrB) can effectively improve insulin resistance and alleviate chronic inflammation, and in order to investigate the therapeutic effect of LrB on polycystic ovary syndrome with insulin resistance (PCOS-IR), we conducted animal experiments. A PCOS-IR rat model was established by feeding a high-fat diet combined with letrozole (1 mg/kg·d for 21 days). The rats were treated with the GPR120 agonists TUG-891 and LrB for 4 weeks. Biochemical parameters (fasting blood glucose, total cholesterol, triglycerides, high- and low-density lipoprotein), hormone levels (serum insulin, E2, T, LH, and FSH), and inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-18) were analyzed. Histopathological analyses of ovaries were performed using hematoxylin/eosin (H&E) staining. Real-time PCR and western blotting were used to assess GPR120, NLRP3, and caspase-1 expression in ovaries, and immunohistochemistry was used to evaluate LKB1 and AMPK protein expression. LrB reduced body weight, Lee's index, ovarian index, ovarian area, and volume in PCOS-IR rats. It lowered fasting blood glucose, serum insulin, and HOMA-IR. LrB decreased total serum cholesterol, triglyceride, and LDL levels and increased HDL levels. It reduced serum T, LH, and LH/FSH and raised serum E2 and FSH levels. LrB downregulated the mRNA and protein expression levels of NLRP3 and Caspase-1, increased the protein and mRNA expression levels of GPR120 in rat ovaries, and increased LKB1 and AMPK protein expression in ovaries, ameliorating ovarian histopathological changes in PCOS-IR rats. Taken together, LrB upregulated GPR120, LKB1, and AMPK protein expression, downregulated NLRP3 and Caspase-1 protein expression, reduced insulin resistance and chronic inflammation, and ameliorated histopathological changes in ovarian tissues in PCOS rats, suggesting its potential as a treatment for PCOS.
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Affiliation(s)
- Jing Wang
- Guangxi Key Laboratory for Applied Fundamental Research of Zhuang Medicine-Key Laboratory Project under Guangxi Health Commission, Guangxi University of Chinese Medicine, Nanning 530001, China (Z.C.); (X.T.)
- Guangxi Higher Education Key Laboratory for the Research of Du-Related Diseases in Zhuang Medicine, Guangxi University of Chinese Medicine, Nanning 530001, China
- Health Science Center, Hubei Minzu University, Enshi 445000, China
| | - Zheng Huang
- Guangxi Key Laboratory for Applied Fundamental Research of Zhuang Medicine-Key Laboratory Project under Guangxi Health Commission, Guangxi University of Chinese Medicine, Nanning 530001, China (Z.C.); (X.T.)
- Guangxi Higher Education Key Laboratory for the Research of Du-Related Diseases in Zhuang Medicine, Guangxi University of Chinese Medicine, Nanning 530001, China
| | - Zhiyong Cao
- Guangxi Key Laboratory for Applied Fundamental Research of Zhuang Medicine-Key Laboratory Project under Guangxi Health Commission, Guangxi University of Chinese Medicine, Nanning 530001, China (Z.C.); (X.T.)
- Guangxi Higher Education Key Laboratory for the Research of Du-Related Diseases in Zhuang Medicine, Guangxi University of Chinese Medicine, Nanning 530001, China
| | - Yehao Luo
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510006, China;
| | - Yueting Liu
- Guangxi Key Laboratory for Applied Fundamental Research of Zhuang Medicine-Key Laboratory Project under Guangxi Health Commission, Guangxi University of Chinese Medicine, Nanning 530001, China (Z.C.); (X.T.)
- Guangxi Higher Education Key Laboratory for the Research of Du-Related Diseases in Zhuang Medicine, Guangxi University of Chinese Medicine, Nanning 530001, China
| | - Huilu Cao
- Guangxi Key Laboratory for Applied Fundamental Research of Zhuang Medicine-Key Laboratory Project under Guangxi Health Commission, Guangxi University of Chinese Medicine, Nanning 530001, China (Z.C.); (X.T.)
- Guangxi Higher Education Key Laboratory for the Research of Du-Related Diseases in Zhuang Medicine, Guangxi University of Chinese Medicine, Nanning 530001, China
| | - Xiusong Tang
- Guangxi Key Laboratory for Applied Fundamental Research of Zhuang Medicine-Key Laboratory Project under Guangxi Health Commission, Guangxi University of Chinese Medicine, Nanning 530001, China (Z.C.); (X.T.)
- Guangxi Higher Education Key Laboratory for the Research of Du-Related Diseases in Zhuang Medicine, Guangxi University of Chinese Medicine, Nanning 530001, China
| | - Gang Fang
- Guangxi Key Laboratory for Applied Fundamental Research of Zhuang Medicine-Key Laboratory Project under Guangxi Health Commission, Guangxi University of Chinese Medicine, Nanning 530001, China (Z.C.); (X.T.)
- Guangxi Higher Education Key Laboratory for the Research of Du-Related Diseases in Zhuang Medicine, Guangxi University of Chinese Medicine, Nanning 530001, China
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Sun S, Liu Y, Li L, Xiong L, Jiao M, Yang J, Li X, Liu W. Unveiling the shared genetic architecture between testosterone and polycystic ovary syndrome. Sci Rep 2024; 14:23931. [PMID: 39397165 PMCID: PMC11471787 DOI: 10.1038/s41598-024-75816-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 10/08/2024] [Indexed: 10/15/2024] Open
Abstract
Testosterone (T) is a critical predictor of polycystic ovary syndrome (PCOS) but the genetic overlap between T and PCOS has not been established. Here by leveraging genetic datasets from large-scale genome-wide association studies, we assessed the genetic correlation and polygenic overlap between PCOS and three T-related traits using linkage disequilibrium score regression and the bivariate causal mixture model methods. The conjunctional false discovery rate (conjFDR) method was employed to identify shared causal variants. Functional annotation of variants was conducted using FUMA. Total T and bioavailable T exhibited positive correlations with PCOS, while sex hormone-binding globulin (SHBG) showed a negative correlation. All three traits demonstrated extensive genetic overlap with PCOS, with a minimum of 68% of T-related variants influencing PCOS. The conjFDR revealed 4 to 6 causal variants within joint genomic loci shared between PCOS and T-related traits. Functional annotations suggested that these variants might impact PCOS by modulating nearby genes, such as FSHB. Our findings support the hypothesis that PCOS is significantly influenced by androgen abnormalities. Additionally, this study identified several causal variants potentially involved in shared biological mechanisms between PCOS and T regulation.
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Affiliation(s)
- Shuliu Sun
- Department of Obstetrics and Gynecology, Northwest Women's and Children's Hospital, Xi'an, 710061, China
| | - Yan Liu
- Department of Obstetrics and Gynecology, Northwest Women's and Children's Hospital, Xi'an, 710061, China
| | - Lanlan Li
- Department of Obstetrics and Gynecology, Northwest Women's and Children's Hospital, Xi'an, 710061, China
| | - Lili Xiong
- Department of Obstetrics and Gynecology, Northwest Women's and Children's Hospital, Xi'an, 710061, China
| | - Minjie Jiao
- Department of Obstetrics and Gynecology, Northwest Women's and Children's Hospital, Xi'an, 710061, China
| | - Jian Yang
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
| | - Xiaojuan Li
- Department of Obstetrics and Gynecology, Northwest Women's and Children's Hospital, Xi'an, 710061, China
| | - Wei Liu
- Department of Obstetrics and Gynecology, Northwest Women's and Children's Hospital, Xi'an, 710061, China.
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Pililis S, Lampsas S, Kountouri A, Pliouta L, Korakas E, Livadas S, Thymis J, Peppa M, Kalantaridou S, Oikonomou E, Ikonomidis I, Lambadiari V. The Cardiometabolic Risk in Women with Polycystic Ovarian Syndrome (PCOS): From Pathophysiology to Diagnosis and Treatment. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1656. [PMID: 39459443 PMCID: PMC11509436 DOI: 10.3390/medicina60101656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 10/03/2024] [Accepted: 10/08/2024] [Indexed: 10/28/2024]
Abstract
Polycystic Ovarian Syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age, with significant variations in presentation characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. Beyond reproductive health, it may also pose crucial long-term cardiometabolic risks, especially for women with specific types of PCOS, contributing to early subclinical cardiovascular atherosclerotic alterations such as endothelial dysfunction, increased arterial stiffness, and coronary artery calcium levels, respectively. Moreover, the precise relationship between clinical cardiovascular disease (CVD) and PCOS remains debated, with studies demonstrating an elevated risk while others report no significant association. This review investigates the pathophysiology of PCOS, focusing on insulin resistance and its link to subclinical and clinical cardiovascular disease. Diagnostic challenges and novel management strategies, including lifestyle interventions, medications like metformin and glucagon-like peptide-1 receptor agonists (GLP-1RAs), hormonal contraceptives, and bariatric surgery, are further discussed. Recognizing the cardiometabolic risks associated with PCOS, a comprehensive approach and early intervention should address both the reproductive and cardiometabolic dimensions of the syndrome.
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Affiliation(s)
- Sotirios Pililis
- Diabetes Center, 2nd Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (S.P.); (A.K.); (E.K.)
| | - Stamatios Lampsas
- Diabetes Center, 2nd Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (S.P.); (A.K.); (E.K.)
- 2nd Department of Ophthalmology, Attikon Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece
| | - Aikaterini Kountouri
- Diabetes Center, 2nd Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (S.P.); (A.K.); (E.K.)
| | - Loukia Pliouta
- Diabetes Center, 2nd Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (S.P.); (A.K.); (E.K.)
| | - Emmanouil Korakas
- Diabetes Center, 2nd Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (S.P.); (A.K.); (E.K.)
| | | | - John Thymis
- 2nd Cardiology Department, Attikon University Hospital, National & Kapodistrian University of Athens, 12462 Athens, Greece; (J.T.)
| | - Melpomeni Peppa
- Diabetes Center, 2nd Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (S.P.); (A.K.); (E.K.)
| | - Sophia Kalantaridou
- 3rd Department of Obstetrics and Gynecology, Attikon Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece
| | - Evangelos Oikonomou
- 3rd Department of Cardiology, Medical School, “Sotiria” Chest Diseases Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Ignatios Ikonomidis
- 2nd Cardiology Department, Attikon University Hospital, National & Kapodistrian University of Athens, 12462 Athens, Greece; (J.T.)
| | - Vaia Lambadiari
- Diabetes Center, 2nd Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (S.P.); (A.K.); (E.K.)
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Roy M, Parveen R, Khan P, Majid H, Pathak M, Saxena R, Nidhi. A systematic review on effect of sodium-glucose cotransporter-2 inhibitors on the metabolic and endocrinological profile of patients with polycystic ovarian syndrome. Expert Opin Pharmacother 2024; 25:1953-1960. [PMID: 39312193 DOI: 10.1080/14656566.2024.2407513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 09/18/2024] [Indexed: 09/26/2024]
Abstract
BACKGROUND Polycystic ovarian syndrome (PCOS) has been a common metabolic and endocrinal disorder, prevalent amongst women belonging to the reproductive age group. The aim of this systematic review was to assess the safety and efficacy profile of sodium-glucose cotransporter 2 (SGLT2) inhibitors (Canagliflozin, Dapagliflozin, Empagliflozin, and Licogliflozin) for the treatment of women suffering from PCOS. METHODS A literature search in PubMed, Science Direct, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov was conducted for randomized clinical trials of SGLT-2 inhibitors in PCOS patients by applying predetermined inclusion and exclusion criteria. The articles in English language were included. RESULTS Four randomized controlled trials including 146 subjects were included in the review. The clinical studies indicated a significant decrease in the levels of total testosterone, free androgen index, total body fat, homeostasis model assessment-estimated insulin resistance (HOMA-IR), body mass index (BMI), dehydroepiandrosterone sulfate (DHEAS) and fasting plasma glucose (FPG). However, no significant difference was reported in levels of sex hormone-binding globulin (SHBG). Overall, there was improvement in metabolic and endocrine profiles, suggesting a potentially beneficial impact of SGLT2 inhibitors in the management of PCOS. CONCLUSION There is a requirement for large extensive clinical trials to demonstrate the efficacy of SGLT-2 inhibitors in PCOS patients.
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Affiliation(s)
- Madhura Roy
- Department of Translational and Clinical Research, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, India
| | - Rizwana Parveen
- Department of Translational and Clinical Research, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, India
| | - Parvej Khan
- Department of Translational and Clinical Research, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, India
| | - Haya Majid
- Department of Translational and Clinical Research, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, India
| | - Mani Pathak
- Department of Translational and Clinical Research, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, India
| | - Rajesh Saxena
- Department of Clinical Research, Max Super Specialty Hospital, New Delhi, India
| | - Nidhi
- Department of Translational and Clinical Research, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, India
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Alessandri G, Mancabelli L, Fontana F, Lepore E, Forte G, Burratti M, Ventura M, Turroni F. Disclosing α-lactalbumin impact on the intestinal and vaginal microbiota of women suffering from polycystic ovary syndrome. Microb Biotechnol 2024; 17:e14540. [PMID: 39364592 PMCID: PMC11450379 DOI: 10.1111/1751-7915.14540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Accepted: 07/17/2024] [Indexed: 10/05/2024] Open
Abstract
Polycystic ovary syndrome (PCOS) is one of the most widespread endocrinopathy affecting women of reproductive age with detrimental effects on life quality and health. Among several mechanisms involved in its aetiopathogenesis, recent studies have also postulated the involvement of the vaginal and intestinal microbiota in the development of this disorder. In this study, an accurate insight into the microbial changes associated with PCOS was performed through a pooled-analysis highlighting that this syndrome is characterized by intestinal and vaginal dysbiosis with a reduction of beneficial microorganisms and a higher proportion of potential pathogens. Based on this observation, we evaluated the ability of a milk-derived protein exerting positive outcomes in the management of PCOS, that is, α-lactalbumin (α-LA), to recover PCOS-related dysbiosis. In vitro experiments revealed that this protein improved the growth performances of members of two health-promoting bacterial genera, that is, Bifidobacterium and Lactobacillus, depleted in both intestinal and vaginal microbiota of PCOS-affected women. In addition, α-LA modulated the taxonomic composition and growth performances of the microbial players of the complex intestinal and vaginal microbiota. Finally, an in vivo pilot study further corroborated these observations. The oral administration of α-LA for 30 days to women with PCOS revealed that this protein may have a role in favouring the growth of health-promoting bacteria yet limiting the proliferation of potential pathogens. Overall, our results could pave the way to the use of α-LA as a valid compound with 'prebiotic effects' to limit/restore the PCOS-related intestinal and vaginal dysbiosis.
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Affiliation(s)
- Giulia Alessandri
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental SustainabilityUniversity of ParmaParmaItaly
| | - Leonardo Mancabelli
- Department of Medicine and SurgeryUniversity of ParmaParmaItaly
- Microbiome Research HubUniversity of ParmaParmaItaly
| | - Federico Fontana
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental SustainabilityUniversity of ParmaParmaItaly
| | | | | | | | - Marco Ventura
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental SustainabilityUniversity of ParmaParmaItaly
- Microbiome Research HubUniversity of ParmaParmaItaly
| | - Francesca Turroni
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental SustainabilityUniversity of ParmaParmaItaly
- Microbiome Research HubUniversity of ParmaParmaItaly
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Austregésilo de Athayde De Hollanda Morais B, Martins Prizão V, de Moura de Souza M, Ximenes Mendes B, Rodrigues Defante ML, Cosendey Martins O, Rodrigues AM. The efficacy and safety of GLP-1 agonists in PCOS women living with obesity in promoting weight loss and hormonal regulation: A meta-analysis of randomized controlled trials. J Diabetes Complications 2024; 38:108834. [PMID: 39178623 DOI: 10.1016/j.jdiacomp.2024.108834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 07/04/2024] [Accepted: 08/05/2024] [Indexed: 08/26/2024]
Abstract
BACKGROUND The efficacy of GLP1 receptor agonists (GLP1-RAs) in treating polycystic ovarian syndrome (PCOS) remains unclear. While GLP1-RAs are known to promote weight loss in patients with diabetes and living with obesity, their impact on weight reduction and hormonal regulation in women with PCOS is understudied. Therefore, we aimed to assess the efficacy of GLP1-RAs in PCOS women living with obesity through a meta-analysis, comparing their effects to placebo. HYPOTHESIS The use of GLP1-RAs in PCOS women living with obesity can reduce body mass index and waist circumference as well as improve hyperinsulinism, and hyperandrogenism as well as normalize total testosterone, total cholesterol and HOMA-IR markers in PCOS women living with obesity. METHODS We systematically searched the PubMed, Cochrane Central, Scopus and Embase databases to identify randomized controlled trials (RCT) comparing GLP1-RAs versus placebo among women diagnosed with PCOS based on the Rotterdam Criteria. Our primary outcomes of interest included body mass index (BMI), triglycerides, waist circumference, total testosterone, total cholesterol, and HOMA-IR. We performed data extraction and quality assessment for studies that met the inclusion criteria. We pooled mean difference (MD) and 95 % confidence intervals (CI) with a random-effect model for continuous endpoints. RESULTS We included 176 participants from four RCTs. Semaglutide and Liraglutide were used in 23 (13 %) and 103 (58 %) participants, respectively. GLP1-RAs use was associated with a significant reduction in waist circumference (MD: -5.16 cm; 95 % CI: -6.11 to -4.21; p ˂ 0.00001), body mass index (BMI) (MD: -2.42; 95 % CI: -3.10 to -1.74; p ˂ 0.00001), serum triglycerides (MD: -0.20; 95 % CI: -0.30 to -0.11; p ˂ 0.00001) and total testosterone levels (MD: -1.33; 95 % CI: -2.55 to -0.12; p = 0.03) when compared to placebo. There was no significant difference in total cholesterol (MD: -0.04; 95 % CI: -0.10 to 0.01; p = 0.15) and HOMA-IR (MD: -0.30; 95 % CI: -0.92 to 0.32; p = 0.35) levels. Adverse events information was available for 112 patients, where 49 had light side effects such as nausea and abdominal pain. CONCLUSION The use of GLP1-RAs demonstrates efficacy in reducing BMI, triglycerides, waist circumference and total testosterone. There was no significant difference in total cholesterol and HOMA-IR levels. These results signify its viability as a favourable treatment option for managing PCOS symptoms in women living with obesity.
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