To analyze and evaluate the correlation between different lipid metabolism levels and endometriosis. The literatures on lipid metabolism and endometriosis published in databases were searched and collected. The search was conducted up to December 2023. The meta-analysis was conducted using Review Manager 5.4.1 software, with odds ratios (ORs) or standardized mean difference (SMD), confidence intervals (CIs), and heterogeneity (I2) being calculated. The literature bias was evaluated by drawing funnel plot. Five hundred and eighty-four literatures were retrieved, and finally, 7 literatures were included in this study. Meta-analysis showed that the level of total cholesterol (TC) in endometriosis groups was higher than control group [SMD = 1.70, 95%CI (0.60-2.80), p = 0.003], while triglyceride (TG) [SMD=-0.24, 95%CI (-0.68-0.21), p = 0.300], low-density lipoprotein (LDL) [SMD = 0.22, 95%CI (-0.34 - 0.78), p = 0.440] and high-density lipoprotein (HDL) [SMD = 0.06, 95%CI (-0.14 - 0.25), p = 0.550] was not statistically significant. Sensitivity analysis indicated that the combined effect size results were stable and reliable [SMD = 1.70, 95%CI (0.60-2.80), p = 0.030]. Funnel plot results showed publication bias. Patients with endometriosis have abnormal blood lipid level, and higher TC level may be a risk factor for endometriosis. The impact of blood lipid metabolism on endometriosis may provide new insights into the pathogenesis and treatment prognosis of endometriosis.

This study investigates the causal associations between interleukin receptor-related factors and the development of endometriosis, as their etiology and pathophysiology remain largely unknown. A two-sample Mendelian randomization (MR) approach was employed to analyze genetic variants associated with interleukin receptor related factors as instrumental variables (IVs). The F-values have to be > 10 to exclude weak instrumental bias. The primary analysis was conducted using the inverse variance weighted (IVW) method, with confirmation using the MR-Egger, weighted median (WM), simple mode, and weighted mode methods. Sensitivity analyses were performed to ensure robustness, including tests for heterogeneity, pleiotropy, and leave-one-out. Multivariable MR (MVMR) analysis was used to assess the direct and mediated effects of immune cells. The results indicated significant causal associations between interleukin receptor factors prot-a-1542 (IL-6Rβ), prot-a-1530 (IL-3Rα), and prot-b-38 (IL-1RL1) and endometriosis. Reverse MR analysis showed that endometriosis did not significantly affect prot-a-1530 or prot-b-38. After adjusting for confounders like body mass index and smoking, these factors retained their significance. Additionally, immune cells(ebi-a-GCST90001951) were found to mediate the relationship between prot-b-38 and endometriosis, with an indirect effect accounting for approximately 6.38% of the total effect. This study provides new insights into endometriosis mechanisms involving specific interleukin receptor factors.

The growing interest in RNA-based therapeutics has positioned small interfering RNA (siRNA) as a promising tool for gene silencing with high specificity and efficacy. However, the successful clinical application of siRNA therapies requires efficient delivery systems to overcome extracellular and intracellular barriers. Chitosan, a naturally derived polysaccharide, has gained significant attention as a non-viral vector due to its biodegradability, biocompatibility, mucoadhesive properties, and capacity to enhance cellular uptake. These attributes make chitosan an attractive alternative to lipid-based nanoparticles, which currently dominate siRNA delivery platforms. Recent advancements in chitosan-based nanoformulations, including chemical modifications and functionalization strategies, have improved siRNA stability, targeting efficiency, and transfection potential, addressing key limitations such as low bioavailability and immunogenicity. Despite these advances, challenges remain in achieving optimal release kinetics, scalability, and consistent therapeutic efficacy. Future research efforts will focus on engineering chitosan derivatives with enhanced physicochemical properties, integrating multifunctional nanocarriers, and refining formulation strategies to bridge the gap between preclinical research and clinical translation. The continued development of chitosan-based siRNA therapeutics holds significant potential for advancing precision medicine and expanding treatment options for a variety of diseases, including cancer, metabolic disorders, and inflammatory conditions.

Ultrasound techniques for diagnosing deep infiltrating endometriosis (DIE) currently lack a quantitative method to assess microstructural heterogeneity in relation to diagnosis and clinical symptoms. This study evaluates Shannon entropy-based radiomics for differentiating DIE lesions from adjacent tissue and correlating these features with pain severity.

In this retrospective cohort study (2020-2024), fertile women with histologically confirmed parametrial endometriosis and high-quality ultrasound images were evaluated. Pain was measured using a 10-cm visual analog scale. Two 25 mm² regions of interest (ROIs) were defined: one within the DIE nodule and one in the adjacent perilesional tissue. Each ROI was analyzed with the Shannon entropy algorithm to assess tissue heterogeneity.

In this study, 148/663 women (22.3%) were diagnosed with parametrial DIE, of whom 52 underwent surgery and were included in the study. DIE was localized in 92.3% in the posterior, in 5.8% in both posterior and anterior, and in 2% in the anterior parametrium. Primary symptoms were menstrual pain (88%) and pain at intercourse (63%). ROI entropy of DIE lesion was lower than that of the perilesional ROI (p = 0.05). The area-under-the-curve (AUC) of Shannon entropy for endometriotic vs. adjacent tissue was 91.36% (95% CI: 84.5%-98.21%). The ROI entropy of the DIE lesion exhibited an inverse correlation with menstrual pain (rho -0.46, CI 95% -0.74/-0.12, p = 0.025), and that of perilesional tissue with chronic pelvic pain (rho -0.41, 95% CI -0.73/- 0.04; p = 0.072).

Entropy analysis distinguishes DIE lesion from perilesional tissue and significantly correlates with menstrual pain.

Endometriosis is a benign gynecological disorder characterized by the abnormal presence of endometrium-like cells, referred to as ectopic tissue, located outside the uterine cavity. Beyond the abnormal proliferation of endometrium-like tissues within and beyond the pelvic cavity, compelling scientific evidence underscores the crucial involvement of the NOD-like receptor NLRP3 inflammasome and pyroptosis in the pathogenesis of EMS. Our investigation has revealed a striking upregulation of the endogenous protein GATA-binding protein 6 (GATA6) in abdominal wall EMS. Notably, the knockdown of GATA6 significantly impaired the viability and migratory potential of primary ectopic endometrial stromal cells (EESCs) while also inhibiting crucial markers of pyroptosis, such as NLRP3, the gasdermin D N-terminal fragment (GSDMD-N), and reactive oxygen species (ROS) levels within these cells. Delving deeper into the underlying mechanisms, we discovered that suppressing GATA6 mitigated the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in EESCs. The administration of 740 Y-P, an agonist of the PI3K/AKT pathway, mitigated the inhibitive actions of GATA6 knockdown on EESCs' growth, migration, and pyroptosis, highlighting the intricate crosstalk between GATA6 and this intricate signaling cascade. In vivo experiments corroborated these findings, demonstrating that reduced GATA6 expression effectively restrained the growth of endometrial lesions and concurrently suppressed pyroptosis, accompanied by a dampening of PI3K/AKT signaling within these lesions. In summary, our study underscores the pivotal role of GATA6 in modulating the growth and pyroptosis of abdominal wall EMS through its regulation of the PI3K/AKT signaling pathway. Silencing GATA6 emerges as a promising approach to alleviate pyroptosis and potentially offers a novel therapeutic angle for managing abdominal wall EMS.

To describe sociodemographic characteristics of women with hospital diagnosed endometriosis in Denmark and compare them with women without endometriosis.

Case-control study using Danish national registers. Cases were identified as women aged 14-84 years receiving a first-time hospital-based diagnosis of endometriosis in 1991-2021 (n = 37.709). Each case was matched based on date of diagnosis and birth year to five controls without endometriosis (n = 188.545). Information on diagnosis of endometriosis and sociodemographic factors was obtained from Danish registers. Descriptive statistics and unadjusted and adjusted conditional logistic regression analyses were used to investigate the association between a diagnosis of endometriosis and sociodemographic factors.

For family-based socioeconomic status, women in all groups other than the employed category (both higher and lower socioeconomic status) had lower odds of receiving a diagnosis (ORs ranging from 0.78 to 0.91). Women with primary education, master or equivalent, and PhD had lower odds of a diagnosis (ORs 0.79-0.93) compared to upper secondary education. Compared to couples, singles and "other" had slightly lower odds of a diagnosis (ORs 0.91-0.94). Women of Danish origin and immigrants had similar odds of a diagnosis whereas descendants had lower odds (0.85 (95% CI: 0.76-0.95)) when compared to the two other groups.

Sociodemographic factors were found to be associated with receiving a hospital diagnosis of endometriosis. However, only smaller differences and a mixed pattern were found.

Uterine scar defects result from poor healing of the hysterotomy after cesarean sections (CS), in multiple cases leading to retroflexio uteri and retrograde menstruation. Endometriosis is the probable consequence. Patients often experience overlapping symptoms such as dysmenorrhea, dyspareunia, and infertility.

This study analysed cases of sonographically detected uterine scar defects, subsequently undergoing laparoscopy at the University Clinic St. Hedwig, in Regensburg, between 2020 and 2024. Herefore, surgery reports were reviewed, focusing on extragenital endometriosis, symptoms of Cesarean Scar Disorder (CSD), niche morphology, uterine position, and endometriosis localisation using the #Enzian classification.

Extragenital endometriosis was histologically confirmed in 45 of 94 patients (47.9 %) with symptomatic or large uterine niches. A significant association was found between endometriosis and heavy menstrual bleeding (HMB) (p < 0.001) as well as retroflexio uteri (p = 0.036). Symptoms related to CSD did not differ in patients with or without Endometriosis. Endometriotic implants were primarily located in the peritoneum behind the uterus and sacrouterine ligaments, supporting the hypothesis of retrograde menstruation.

There is significant overlap between the symptoms of endometriosis and CSD. Almost half of the patients with a symptomatic niche were found to have endometriosis, whereby the location of endometriosis supports the hypothesis of retrograde menstruation. However, the patient´s history of complaints is not indicative of the diagnosis of endometriosis. Therefore, all patients with CSD should be offered a laparoscopy and endometriosis surgery. All patients with a previous caesarean section presenting with symptoms of endometriosis should be offered standardised and high-quality niche diagnosis and treatment.

Alongside being contraceptives, progestins have been investigated as potential anti-inflammatory and analgesic therapies for use in painful gynaecological conditions. This review aims to synthesise evidence pertaining to the efficacy of progestins as analgesics for use in endometriosis, fibroids and pre-menstrual syndrome (PMS).

We conducted a systematic review of the extant literature investigating the analgesic efficacy of progestins compared to any comparator interventions for individuals with the three specified gynaecological conditions. The search was carried out across the PubMed and CENTRAL databases on 7 April 2024 for randomised control trials (RCTs) published in the peer-reviewed literature from 2000 onwards. Data pertaining to analgesic efficacy, assessed by changes in pain indices/scores before and after treatment, were synthesised narratively. Data pertaining to adverse effect frequency and changes in bone mineral density (BMD) were also synthesised narratively. Risk of bias was assessed using the Cochrane risk of bias 2 tool.

The primary search identified 1220 potentially eligible RCTs of which 21 were ultimately included; 19 RCTs related to endometriosis, two related to fibroids and zero related to PMS. Quality assessment identified nine studies to be at a low risk of bias, nine studies with some concerns surrounding bias and three studies to be at a high risk of bias. The included studies represented a total of 2745 participants of whom 1317 were treated with a progestin and 1428 received a comparator intervention. In 18 of the 19 studies concerning endometriosis, progestins produced a statistically significant reduction in pain, further, in five instances progestins were more efficacious in reducing pain than comparator interventions. In both studies on fibroids, progestins produced significant reductions in pain, however, statistically significant differences compared to comparator interventions were not demonstrated. The most frequently cited adverse effect of progestins was spotting/irregular bleeding whilst those receiving comparator interventions most often reported hot flushes; cited in 12 and seven studies respectively. Five studies assessed the impact of progestins and comparators on BMD. Three studies found progestins significantly reduced BMD, however, in these instances reductions were significantly lower than those produced by comparator interventions and in two studies were not statistically significant after 12 months of follow-up.

Our review demonstrates the potential scope for the use of progestins as analgesics in the management of pain associated with endometriosis. Further research will need to be conducted to identify their efficacy in the management of pain associated with fibroids and PMS.

Endometriosis (EMS) is a difficult gynecological disease to cure. Frizzled-7 (FZD7) has been shown to be associated with the development of EMS, but its specific mechanism remains unclarified. This study aims to explore the role of FZD7 in EMS.

RT-qPCR and western blot were used to detect the expression level of FZD7 in human endometrial stromal cells (hESCs) and human ectopic endometrial stromal cell line hEM15A. The interfering plasmid of FZD7 was established. CCK-8, EdU, wound healing, transwell invasion, and cytoskeletal staining assays were applied to evaluate the role of FZD7 silencing in hEM15A cell proliferation, invasion, and migration. Tube forming ability of cells was evaluated by tube formation assay. Cellular VEGF, GSH, and MDA levels were measure by kits. Intracellular lipid ROS and Fe2+ levels were tested using C11-BODIPY (581/591) and FeRhoNox-1 probes, respectively. The ferroptosis-related protein SLC7A11, GPX4, and ACSL4 expressions were analyzed using western blot. The effects of ferroptosis on endometriotic cell viability, migration, and angiogenesis were further analyzed with the addition of an ferroptosis inhibitor (Fer-1).

FZD7 was upregulated in hEM15A cells, and silencing of FZD7 inhibited cell proliferation, migration, invasion, and angiogenesis abilities. Downregulation of FZD7 decreased cellular GSH level and elevated MDA level. Knockdown of FZD7 also caused an increase in intracellular ROS and Fe2+ levels, as well as the downregulation of SLC7A11 and GPX4 levels and the upregulation of ACSL4 level, which are hallmarks of ferroptosis. However, the inhibitory effects of FZD7 knockdown on hEM15A cell progression were reversed when ferroptosis inhibitor Fer-1 added.

The above indices suggest that FZD7 knockdown regulates endometriotic cell proliferation, invasion, migration, and angiogenesis via ferroptosis.

Endometriosis (EMs) is a disease that adversely affects women's health. Immune imbalance is an important factor contributing to EMs, and exosomes (Exo) play an important role in immunomodulation. The purpose of this study was to investigate the effect of exosomes derived from the blood of patients with EMs on macrophage polarization and elucidate the underlying mechanisms. Exosomes were isolated from the serum of healthy controls (control exosomes) and patients with EMs (EMs exosomes). Macrophage polarization levels were detected using flow cytometry (FCM), RT-qPCR, and Western blot. Subsequently, we used RNA sequencing to analyze differential microRNAs (miRNA) and associated pathways. Electroporation techniques were used to modify the exosomes. The associated pathways were analyzed by Western blot. Finally, 12Z cells were co-cultured with macrophages of different polarizations, and the viability and metastasis of 12Z cells were calculated by cell counting kit-8 (CCK-8), scratch, and Transwell. EMs exosomes induced M2-type polarization in macrophages. RNA sequencing results showed that miR-196a-5p was dramatically decreased in EMs exosomes, whereas overexpression of miR-196a-5p in EMs exosomes could inhibit the M2-type polarization of macrophages and activate the Hippo pathway. In addition, M2-type macrophages promoted 12Z cell proliferation and metastasis. These findings suggest that serum-derived exosomes encapsulating miR-196a-5p alleviate endometriosis by promoting M1-type macrophage polarization via Hippo pathway activation.

Although thoracic endometriosis (TE) represents the most common manifestation of extra-pelvic endometriosis, it is a rare condition and currently there is no established clinical guideline for the management of this condition. The study's primary objective was to assess patient satisfaction with the treatment provided. A secondary objective was to investigate the efficacy of different treatment modalities in terms of symptom and lesion recurrence.

A retrospective review of the clinical records of all women with TE who had been referred to our institution, a tertiary referral center, was conducted between January 2000 and September 2021. A frequency analysis was performed for all the variables examined in the study. The Kaplan-Meier method was adopted to analyse the time from thoracic surgery to PNX recurrence. Lastly, an intention-to-treat analysis was performed.

Regarding clinical presentation, 50% of women (30/60; 95% CI 36.8-63.2) experienced at least one episode of pneumothorax (PNX). A total of 61.7% of the women in the study underwent surgical intervention, while 36.6% received pharmacological treatment. The cumulative recurrence rate of the first PNX following surgery was 0.26 (0.13-0.41) and 0.82 (0.44-0.95) at six months and 240 months, respectively. At the follow-up assessment, regardless of the administered treatment modality, over half of the women included in the study reported being satisfied with their treatment (PGIC). Additionally, most of them described their overall condition as having improved since the onset of the treatment (PGIS).

Both surgical and pharmacological treatments are valuable options for TE. Rather than being considered mutually exclusive, these approaches should be viewed as complementary.

The widespread environmental prevalence of tire-derived N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and 6PPD-quinone (6PPD-Q) has provoked public concern about their health risks. This study aimed to investigate the potential of 6PPD and 6PPD-Q to induce endometrial cell dysfunction through nuclear estrogen receptor (ER) and G-protein-coupled estrogen receptor (GPER) signaling pathways. Fluorescence competitive binding and reporter gene assays revealed that 6PPD and 6PPD-Q selectively bound to ERα (not ERβ) and activated ER transcriptional activity, with the lowest observed effective concentrations (LOECs) of 500 and 10 nM, respectively. Calcium mobilization assays further demonstrated that both 6PPD and 6PPD-Q activated the GPER nongenomic pathway in a concentration-dependent manner (LOEC = 1 nM). 6PPD-Q exhibited stronger ERα and GPER activation potency than 6PPD, which was explained well by molecular dynamics simulation. 6PPD and 6PPD-Q stimulated endometrial cell proliferation via ERα/GPER signaling pathways, mechanistically linked to Cyclin D1/Ki67 upregulation. Furthermore, 6PPD/6PPD-Q promoted endometrial cell migration through an ERα/GPER-regulated epithelial-mesenchymal transition and inflammatory responses. Notably, the LOECs for these functional disruptions reached nanomolar levels relevant to human exposure. Collectively, we elucidated the molecular initial events and downstream key events of 6PPD/6PPD-Q-induced endometrial cell dysfunction, which implied their threat to the reproductive system and provided novel perspectives for their health risk evaluation.

Endocrine disrupting chemicals (EDCs) are ubiquitous in the environment and have been shown to interfere with the endocrine system, leading to adverse effects on reproductive health. In females, EDC exposure has been linked to menstrual irregularities, infertility, and pregnancy complications. Epigenetic regulation, which involves modifications to DNA and histones that do not alter the underlying genetic code, plays a crucial role in female reproduction. EDCs have been shown to disrupt epigenetic mechanisms, leading to changes in gene expression that can have long-term effects on reproductive outcomes. Several EDCs, including bisphenol A (BPA) and phthalates, dioxins, and polychlorinated biphenyls (PCBs), have been shown to alter DNA methylation patterns and histone modifications in female reproductive tissues. These changes can lead to altered expression of genes involved in ovarian function, implantation, and placental development. Here, we integrate epidemiological and experimental evidence from the last 20 years to profile the types of diseases that EDCs trigger in the female reproductive system in relation to the uterus, and the corresponding molecular mechanisms that have been studied. In addition, this review will outline the state of knowledge of EDC epigenetic regulation in the uterus and how it impacts reproductive health, as well as identify areas for future research.

The association of lipid accumulation product (LAP) and the likelihood of endometriosis prevalence has not been previously mentioned. The research aimed to assess the possible potential association between LAP and endometriosis in nationwide research. This cross-sectional analysis was conducted on 2,216 participants selected from the National Health and Nutrition Examination Survey (NHANES) in the 1999-2006 cycles. Logistic regression and stratified analysis by age, race, level of education, BMI, marital status, PIR, glycohemoglobin, drinking, and smoking status were used to analyze the association of the LAP index and odds of endometriosis prevalence. Moreover, smoothed curve fitting was used to evaluate the relevancy of LAP and endometriosis. The multivariate logistic regression model showed a positive association between ln LAP and endometriosis. This trend remained after a full adjustment (odds ratio = 1.37, 95% confidence interval:1.08-1.75, P = 0.010). Compared to the minimum ln LAP quartile, participants in the highest ln LAP had a 93% higher chance of endometriosis incidence (odds ratio = 1.93, 95% confidence interval: 1.08-3.46, P = 0.027). After conducting subgroup analysis and interaction testing, it was found that this positive association was most prominent among women aged 35 years and above and participants with glycohemoglobin≥6%. This nationwide study suggested that an elevated ln LAP was related to an increased endometriosis prevalence. Therefore, LAP may be a valuable tool for predicting the occurrence of endometriosis. Follow-up studies are critical to assess the association between LAP and odds of endometriosis prevalence and explain the potential mechanisms of this relationship.

To evaluate the effectiveness of various medications for the treatment of endometriosis-related pain through a network meta-analysis.

A comprehensive search was conducted in PubMed, Embase, Web of Science, and the Cochrane Controlled Trials Register until July 22, 2024. We also searched ClinicalTrials.gov for additional data on recently completed trials or potentially eligible randomized controlled trials (RCTs) but found nothing.

The analysis included randomized RCTs that used pharmacologic interventions for managing endometriosis-related pain. The primary efficacy outcome was endometriosis-associated pelvic pain, which included dysmenorrhea, dyspareunia, and nonmenstrual pelvic pain. The analysis adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines.

A total of 31 RCTs involving 8,665 patients were included in the analysis. In terms of endometriosis-associated pelvic pain, four interventions demonstrated significantly greater efficacy compared with placebo: leuprolide combined with combined oral contraceptive pills (OCPs) (standardized mean difference [SMD] -1.40, 95% CI, -2.41 to -0.38), dienogest (SMD -1.20, 95% CI, -1.78 to -0.61), leuprolide alone (SMD -1.05, 95% CI, -1.64 to -0.45), and combined OCP (SMD -0.67, 95% CI, -1.25 to -0.09). Leuprolide combined with combined OCP emerged as the most effective treatment modality. In addition, elagolix and the combination of vitamin C and vitamin E were identified as the most effective interventions for dysmenorrhea and dyspareunia. For nonmenstrual pelvic pain, gestrinone demonstrated superior efficacy compared with placebo and all other interventions.

This network meta-analysis indicates that leuprolide in combination with combined OCP, elagolix, vitamins C and E, and gestrinone may represent the most effective therapeutic options for alleviating endometriosis-associated pelvic pain, dysmenorrhea, dyspareunia, and nonmenstrual pelvic pain. These findings enhance our understanding of the relative efficacy of treatment strategies for pain associated with endometriosis. Future research should focus on conducting larger-scale and rigorously designed clinical trials within the target patient populations to further validate these results.

Background: This study investigates the impact of ovarian endometriosis on pregnancy outcomes. Methods: A retrospective analysis was conducted at Etlik Zübeyde Hanım Women's Diseases Training and Research Hospital between January 2019 and December 2024, including 1127 pregnant women-170 with ovarian endometriosis and 957 healthy controls. Pregnancies achieved via assisted reproductive techniques were excluded. Statistical analyses were performed using appropriate tests, and a p-value < 0.05 was considered significant. Results: Women with ovarian endometriosis had higher rates of miscarriage (21.8% vs. 7.5%), preterm birth (15.0% vs. 8.8%), and placenta previa (4.7% vs. 0.6%), with adjusted odds ratios (OR) of 3.41, 1.84, and 7.82, respectively. No significant differences were observed in terms of gestational diabetes, hypertensive disorders, fetal growth restriction (FGR), intrahepatic cholestasis of pregnancy (ICP), placental abruption, or preterm premature rupture of membranes (PPROM). Cyst size and bilaterality were not associated with complications. Conclusions: Spontaneously conceiving women with ovarian endometriosis are at increased risk for miscarriage, placenta previa, and preterm birth. Prospective randomized studies are warranted to validate these findings.

Background and Objectives: Dysbiosis of the oral-gut axis is related to several extraintestinal inflammatory diseases, including endometriosis. This study aims to assess the microbial landscape and pathogenic potential of distinct biological niches during endometriosis. Materials and Methods: A microbiome meta-analysis was conducted on 182 metagenomic sequences (79 of fecal and 103 of vaginal origin) from women with and without endometriosis. Fecal and vaginal microbial diversity, differential abundance, and functional analysis based on disease status were assessed. Random forest, gradient boosting, and generalized linear modeling were used to predict endometriosis based on differentially enriched bacteria. Results: Only intestinal microbes displayed distinctive taxonomic and functional characteristics in women with endometriosis compared to control women. Taxonomic differences were quantified using the microbial endometriosis index (MEI), which effectively distinguished between individuals with and without the disease. The observed functional enrichment pointed to proinflammatory pathways previously related to endometriosis development. Conclusions: Dysbiosis in the oral-gut microbial community appears to play a prevalent role in endometriosis. Our findings pave the ground for future studies exploring the potential mechanistic involvement of the oral-gut axis in disease pathogenesis.

Introduction: Pain perception and management differ by sex, with women frequently experiencing more acute and chronic pain and greater disability than men. Yet, anesthesiology and pain control often overlook the physiological, hormonal, and psychological factors shaping women's pain. Methods: This narrative review explores essential considerations from current literature to optimize pain management in women. We examine evidence about the impact of hormonal changes, reproductive transitions, and psychosocial factors on pain perception and responses to analgesics. By highlighting key insights and practical strategies, we aim to support the development of personalized pain management approaches tailored to women's unique needs. Results: Hormonal changes, including variations in estrogen and progesterone levels, significantly influence pain thresholds and the effectiveness of analgesics and anesthetics. The menstrual cycle, menopausal transitions, and pregnancy each alter pain responses, necessitating personalized approaches to pain management. Postmenopausal women are particularly vulnerable to chronic pain conditions, such as those associated with osteoporosis, which require adjustments in long-term treatment strategies. Furthermore, psychosocial factors like anxiety and emotional distress can intensify pain, highlighting the need for holistic, integrative care. Conclusions: The existing gaps in women's pain management across the lifespan highlight the need to revise both anesthesia and pain management protocols to better account for sex-specific biological and psychosocial factors. Addressing the unique biological and psychosocial factors that influence pain in women can enhance both the effectiveness and equity of care. By tailoring treatment strategies in women, clinicians can not only enhance pain management but also greatly improve their overall quality of life.

Endometriosis is a disease where vascularised tissue similar to endometrium (the lining of the uterus) grows outside of the uterus. Its pathogenesis involves a complex interplay of inflammation, angiogenesis, cellular proliferation, reactive oxygen species (ROS) production, altered energy metabolism, and epithelial-to-mesenchymal transition (EMT).Even though endometriosis was described more than 150 years ago, we have been unable to find its effective therapy. Conservative treatment approaches like non-steroidal anti-inflammatory drugs or hormone therapy are available to date for the treatment of endometriosis. Anti-angiogenic inhibitors and immunomodulators like IFN-α, β, and TNF-α inhibitors are also potential treatment options. These treatments are inadequate as they either affect the symptoms only of endometriosis or target only one pathological pathway involved. Surgical excision of the endometriotic lesion is also possible, however, recurrence of the disease is reported in several cases. A single therapeutic agent targeting several pathological processes in endometriosis would always be a better option. Here we present our perspective on the pharmacological potential of Ethyl pyruvate and also propose it as a promising therapeutic agent for endometriosis as it inhibits inflammation, cell proliferation, angiogenesis, aerobic glycolysis, EMT, and ROS activity together.

Clear cell carcinoma (CCC) is an uncommon malignancy accounting for ∼12% of ovarian carcinomas. Most cases arise from endometriosis, frequently an endometriotic cyst. We report a series of 6 cases where clear cell proliferations, morphologically, and immunophenotypically consistent with CCC, involve the epithelial lining of an endometriotic cyst without invasion into the surrounding stroma. The patients were aged 29 to 63 years (mean 45). In all cases, epithelial proliferations composed of cells with atypical nuclei, sometimes with a hobnail morphology, and clear or eosinophilic cytoplasm involved the epithelial lining of an ovarian endometriotic cyst. In areas, the proliferations comprised a monolayer, but in all cases, there was also significant epithelial stratification and multilayering, sometimes with a pseudopapillary architecture. There was no invasion of the atypical cells into the surrounding ovarian stroma. The proliferations were positive for Napsin A (6 of 6; 4 diffuse, 2 focal), racemase (5 of 5; 3 diffuse, 2 focal), hepatocyte nuclear factor 1-beta (5 of 5; all diffuse), oestrogen receptor (5 of 6; 2 diffuse, 3 focal), and PAX8 (3 of 3; all diffuse). p53 was wild-type in all 6 cases and WT1 and progesterone receptor were negative in the 4 and 6 cases tested, respectively. Mismatch repair immunohistochemistry was retained in the 3 cases tested. Next-generation sequencing was performed in 2 cases. In 1 case, a sole pathogenic MSH6 variant (p.Ser65fs) was identified. Follow-up (2 to 24 months) was available in 5 cases and there was no tumour recurrence. In reporting these "early" clear cell proliferations in endometriotic cysts, we provide recommendations for the reporting pathologist regarding the most appropriate terminology, which is important in patient management. We suggest that these proliferations be termed "CCC in situ" and that identification of such a lesion should prompt extensive sampling in order to exclude an invasive CCC component within the stroma outside the endometriotic cyst lining. We also stress the importance of close dialogue between the pathologist and the clinician and between the clinician and the patient in order to avoid overtreatment in such cases.

To identify key genes and potential drug targets for ovarian-related diseases through genome-wide Mendelian randomization (MR) and colocalization analyses.

We conducted a comprehensive two-sample MR analysis to estimate the causal effects of blood expression quantitative trait loci (eQTLs) on ovarian-related diseases, followed by colocalization analyses to verify the robustness of the expression instrumental variables (IVs). Phenome-wide association studies (PheWAS) were also performed to evaluate the horizontal pleiotropy of potential drug targets and possible side effects.

Large cohorts of European ancestry.

The exposure in this study was the genetic variants (eQTLs) associated with gene expression levels, considered a form of lifelong exposure. Expression quantitative trait loci data were obtained from the eQTLGen Consortium, encompassing 16,987 genes and 31,684 cis-eQTLs derived from blood samples of healthy individuals of European ancestry.

The primary outcome measures were the identification of genes causally associated with ovarian-related diseases and the validation of these genes as potential therapeutic targets.

Our study revealed that specific genes such as CD163L1, PPP3CA, MTAP, F12, NRM, BANK1, ZNF66, GNA15, and SLC6A9 were associated with ovarian endometriosis, ovarian cysts, and polycystic ovarian syndrome. Through MR and colocalization analyses, we identified potential drug targets, including CTNNB1, PTPN7, and ABCB4, with strong evidence of colocalization with ovarian-related diseases. Sensitivity analyses confirmed the robustness of our findings, showing no evidence of horizontal pleiotropy or heterogeneity.

This research highlights the significance of precision medicine approaches in identifying genetic factors underlying ovarian-related diseases and provides a foundation for developing targeted therapies, enhancing diagnostic accuracy, and improving treatment strategies for ovarian-related diseases.

Endometriosis is one of the most common chronic diseases in women, with a prevalence of up to 10%. The disease particularly affects women of reproductive age. Endometriosis has a significant impact on the patient's quality of life (QoL). In the current study, we aimed to evaluate the role of early diagnosis of endometriosis on patients' QoL.

In this longitudinal prospective study, 205 women with endometriosis who were referred to the gynecology department of Amir al-Mominin Hospital (Zabol-Iran) in 2021 were evaluated. Patients were divided into two groups based on the time of diagnosis, including early diagnosis and late diagnosis. An Endometriosis Health Profile (EHP) questionnaire was used to collect information about QoL before and 18 months after treatment. Data were analyzed using SPSSv.26 software and significance level was considered less than 0.05.

In both groups with early and late diagnosis, the QoL scores improved without significant difference (p = 0.303). There was a significant difference between lower stages (1 and 2) and higher stages (3 and 4) in terms of treatment effects on patients' QoL, and higher stages of endometriosis affected patients' QoL before and after treatment more than lower stages (P values < 0.05).

Early or late diagnosis of endometriosis doesn't affect patients' QoL and patients benefit from treatment regardless of the time of diagnosis.

Ovarian endometriosis(OEM) is the most common type of endometriosis, but there is still a lack of simple and easy-to-promote animal models. Therefore, it is necessary to establish a feasible animal model of OEM and analyze its pathogenesis. In this study, a novel insertional surgical method was used to construct the OEM rat model. The rat model group's morphology and HE staining revealed a close relationship between the transplanted ectopic tissue and the ovary. Compared to the surgery group and the normal group, the bilateral OEM group's level of Anti-mullerian hormone(AMH) was noticeably lower. There was no discernible difference in the unilateral OEM group's AMH level between the normal and sham operation groups. Serum interleukin-1beta(IL-1β) levels in four groups of rats showed bilateral OEM had the greatest level, followed by unilateral OEM. Compared to the normal group, the two model groups had greater serum levels of IL-1β. According to immunohistochemistry, unilateral OEM had higher Intercellular adhesion molecule 1(ICAM1), Matrix metalloproteinase-9(MMP9), Tumor necrosis factor-α(TNF-a), and IL-1β expression levels than the normal rat endometrium. WB revealed that bilateral and unilateral ectopic tissues had higher levels of MMP9, TNF-a, Vascular endothelial growth factor D and IL-1β expression than normal tissues. Transcriptome research revealed that ectopic tissues had higher pro-inflammatory, immunological, and ectopic endometrial proliferation pathways than normal tissues. The ovaries of unilateral OEM have down-regulated immune and inflammation-related pathways and up-regulated steroid hormones compared to normal ovarian tissue. GSEA enrichment analysis comparisons between rat and human endometriotic tissue revealed that Janus kinase-signal transducer and activator of transcription(JAK-STAT), Nuclear factor-kappa B(NFκB), and Toll-like receptors were up-regulated. The intercalation approach of OEM building used in this work is more akin to the human OEM lesion type. It deserves promotion that modeling is more straightforward and has a higher success rate than the suture approach.

To investigate the impact of war situation on physical functioning, mental health status, and disease manifestations among endometriosis patients. Questionnaire-based study analyzing physical and psychosocial well-being. The study includes 50 endometriosis patients at Sheba Medical Center who completed a detailed questionnaire before and after the onset of the October 7, 2023, War in Israel. Significant deterioration in physical and mental health after the onset of war (pain score 6 vs 7; p < 0.001). Although having a first-degree relative affected by the war was associated with health deterioration (OR, 5.44; p = 0.02), similar pattern of health status aggregation was observed also in a subgroup of 19 women without family involvement, suggesting the general war situation as a likely cause. Starting new anti-anxiety or antidepressant medications and psychological therapy had a protective effect (OR, 0.21; p = 0.05). War situation exacerbates endometriosis symptoms, highlighting the importance of early psychological interventions to mitigate negative impacts.

Endometriosis is a chronic gynecological disorder affecting millions of women worldwide, causing chronic pelvic pain, dyspareunia, dysmenorrhea, and infertility, and severely impacting their quality of life. Treatment primarily involves hormonal therapies and surgical excision, but high recurrence rates and the economic burden are substantial. With these challenges, significant discussion surrounds the potential role of dietary patterns in managing endometriosis, making it necessary to bridge this critical gap. This review investigates the current scientific evidence on the dietary patterns (eg, Mediterranean, vegetarian, anti-inflammatory, low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols [low-FODMAP], and Western-style diets) associated with endometriosis and provides a concise, yet thorough, overview on the subject. In addition, antioxidants, microbiota, and artificial intelligence (AI) and their potential roles were also evaluated as future directions. An electronic-based search was performed in MEDLINE, Embase, Cochrane Library, CINAHL, ClinicalTrials.gov, Scopus, and Web of Science. The current data on the topic indicate that a diet based on the Mediterranean and anti-inflammatory diet pattern, rich in dietary fiber, omega-3 fatty acids, plant-based protein, and vitamins and minerals, has a positive influence on endometriosis, yielding a promising improvement in patient symptoms. Preclinical investigations and clinical trials indicate that dietary antioxidants and gut microbiota modulation present potential new approaches in managing endometriosis. Also, AI may offer a promising avenue to explore how dietary components interact with endometriosis. Ultimately, considering genetic and lifestyle factors, a healthy, balanced, personalized approach to diet may offer valuable insights on the role of diet as a means of symptom improvement, facilitating the utilization of nutrition for the management of endometriosis.

The unique physiological structure of women has led to a variety of diseases that have attracted the attention of many people in recent years. Disturbances in the reproductive system microenvironment lead to the progression of various female tumours and pregnancy disorders. Numerous studies have shown that epigenetic modifications crucially influence both oogenesis and foetal development. m6A, a modification at the mRNA level, consists of three parts, namely, writers, erasers, and readers, which are involved in several biological functions, such as the nucleation and stabilisation of mRNAs, thereby regulating the development of reproductive system diseases. In this manuscript, we delineate the constituents of m6A, their biological roles, and advancements in understanding m6A within the maternal-foetal immunological context. In addition, we summarise the mechanism of m6A in gynaecological diseases and provide a new perspective for targeting m6A to delay the progression of reproductive system diseases in clinical practice.

Endometrial thickness plays an important role in successful embryo implantation and normal pregnancy achievement. However, a thin endometrial layer (≤ 7 mm) may have a significant effect on microenvironment tolerance, which is further related to successful embryo implantation or conception, either naturally or after assisted reproductive technology. Moreover, this microenvironment tolerance shift induces hypoxic damage to endometrial epithelial cells (EECs), which results in altered signaling biomolecule secretion, including exosome content. In the context of endometrium regeneration, mesenchymal stromal cells (MSCs) and umbilical cord (UC)-derived stem cells have been applied in clinical trials with promising results. It has been recently shown that exosomes derived from hypoxic damaged EECs directly contribute to the increased migratory and regenerative abilities of UCs and MSCs. Specifically, microRNAs in exosomes secreted by the hypoxic damaged EECs, such as miR-214-5p and miR-21-5p, play a crucial role in the migratory capacity and differentiation ability of MSCs to EECs mediated through the signal transducer and activator of transcription 3 (STAT3) signaling pathway. Taking into consideration the above information, UC-MSCs may be considered as a modern intervention for endometrial regeneration.

Endometriosis is a devastating chronic condition with significant physical and social implications. This research focused on two questions: 1) how do endometriosis patients experience healthcare in Canada, and 2) how can the healthcare encounter effectively address the psychosocial burden of disease that patients bear? This study examines the psychosocial implications of endometriosis diagnosis and treatment. Data was obtained through semi-structured interviews with nine people diagnosed with endometriosis. Interview questions centering patient perceptions of care were thematically analyzed utilizing reflexive thematic analysis. Analyzing participant narratives and drawing upon Kleinman's concepts of illness experiences and slow medicine, this article underlines the urgency of moving toward a deeper ethics of care for endometriosis patients, wherein the patient is understood and advocated for within the Canadian healthcare system. Drawing upon participant experiences, the present research calls for the widespread availability of a comprehensive healthcare model for the treatment of endometriosis.

Endometriosis affects women of reproductive age. Increasing attention is being given to the characterization of comorbidities in endometriosis to enhance clinical phenotyping. Among these comorbidities, migraine has been reported to be significantly more common in individuals with endometriosis compared to the general population. However, the true epidemiological burden remains uncertain, and no conclusive evidence links specific subtypes of endometriosis to migraine.

Seven electronic databases were searched from inception until July 22nd, 2024, using combinations of relevant keywords. PROSPERO Registration CRD42023449492. Two independent reviewers screened the records according to inclusion/exclusion criteria and abstracted data. The risk of bias assessment was undertaken using the ROBINS-E tool. Random effects models were implemented to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between endometriosis and migraine. Fourteen studies were included in the qualitative synthesis, and 13 in the meta-analysis, accounting for a total of 331,655 individuals (32,489 with endometriosis vs. 299,166 controls). There was a serious risk of bias in the majority of the included studies, with 50% being at very high risk of bias. The risk of migraine was higher in individuals with endometriosis compared to those without (OR 2.25, 95%CI = 1.85-2.72; n = 13 studies; I2 = 81%). This association remained significant in the sensitivity analyses: (i) when excluding studies at very high or high risk of bias (OR 2.64; 95%CI = 1.62-4.31; n = 4 studies; I2 = 77%), (ii) when including only risk estimates adjusted for clinically relevant confounders (OR 2.35; 95%CI = 1.77-3.13; n = 6 studies; I2 = 88%), and (iii) when including only risk estimates adjusted for hormonal therapy (OR 1.95; 95%CI = 1.42-2.66; n = 3; I2 = 92%). Endometriosis was significantly associated with migraine without aura (OR 2.64, 95%CI 1.89-3.69; n = 3 studies; I2 = 0%), but not migraine with aura (OR 3.47, 95%CI = 0.53-22.89; n = 3, I2 = 73%).

This meta-analysis highlights the high prevalence of migraine in patients with endometriosis. However, due to observed high heterogeneity and risk of bias, caution is advised when interpreting and applying these findings in clinical practice. Future research should address these issues by limiting variations in diagnostic criteria, stratifying study populations, accounting for key confounders, and investigating potential underlying pathophysiological mechanisms to enhance understanding of the endometriosis-migraine relationship.

Intrauterine devices (IUDs) are drug-device combination products that are placed inside the uterus above the endometrium. IUDs contain a therapeutic agent used for contraception and have been shown to have other therapeutic benefits. Over the past century, intrauterine drug delivery systems (IUDDS) have revolutionized women's health, and they hold immense growth potential in the future for new developments in the therapeutic areas beyond contraception.

The aim of this review is to offer a comprehensive description of the history, development, and current state of IUDDS, next-generation IUDDS, and future applications of IUDDS in therapeutic areas beyond contraception such as multi-purpose prevention technologies, hormone replacement therapy, endometriosis, uterine fibroids, and endometrial cancer.

The uterus's unique features make it an ideal site for controlled, prolonged, and localized delivery of drugs, ensuring maximum concentration at the target site. Currently, IUDs are the most widely used contraceptive method. Future IUDDS hold the potential to deliver therapeutic agents for broader therapeutic areas for women's health, potentially aiding in the treatment of various diseases and disorders of the female reproductive system. Further research in development, characterization, and translation is warranted to ensure IUDDS reach their potential in many areas of women's health.

Exposure to PM2.5 (particulate matter <2.5 μm) has been implicated in increasing the risk of endometriosis and worsening its symptoms. However, the molecular mechanisms and direct associations remain unclear. This study explored whether PM2.5 contributes to the onset or progression of endometriosis using in vitro and in vivo models. Endometrial (EM) cells from women without endometriosis were cultured to the second passages (P2) with or without exposure to PM2.5 at a concentration of 200 µg/ml (N = 5 for each group). Z-stack confocal imaging confirmed PM accumulation in the nucleus and cytoplasm of exposed EM cells. Initial PM exposure at the primary passage (P0) led to decreased proliferation, migration, anti-apoptosis, and oxidative stress, accompanied by downregulation of associated pathways. However, repeated PM exposure during subculturing to P2 led to increased proliferation, enhanced anti-apoptotic activity, and elevated oxidative stress. Given the similarity of these gene expression alterations to those observed in endometriosis, an endometriosis-induced mouse model was established to assess the potential of repeated PM exposure to exacerbate the condition in vivo. To investigate the in vivo effects, an endometriosis-induced mouse model was developed using female C57BL/6 mice exposed to low (10 mg/kg/day) or high (20 mg/kg/day) doses of PM2.5 for 4 weeks (n = 6 for each group). PM exposure significantly enlarged endometriotic lesions compared to controls (no PM exposure). Upregulated gene expression in endometriotic lesions included anti-apoptotic (Bcl2/Bax), proliferative (p-ERK), inflammatory (p-NF-κB, p-c-jun, IL-6, IL-1β), and migration (MMP-2, MMP-9) markers. PM exposure altered estrogen receptor (ER) expression, resulting in a decreased ERα/ERβ ratio in both dose groups. The control group exhibited a ratio of 1.03 ± 0.09, while the low-dose and high-dose mice had ratios of 0.57 ± 0.08 (P = 0.02) and 0.46 ± 0.26 (P = 0.03), respectively. In conclusion, PM2.5 exposure alters gene expression related to cell growth, survival, oxidative stress, and migration in EM cells and exacerbates endometriotic lesions in vivo, likely through ER modulation. These findings suggest PM2.5 may contribute to other estrogen-dependent conditions, such as leiomyoma or adenomyosis, by influencing ER pathways.

Ovarian endometriosis (OEM) is a chronic inflammatory condition that impairs ovarian function. While its effects on ovarian reserve are well established, the long-term consequences of OEM on ovarian dysfunction, premature ovarian failure (POF), and systemic health, particularly in the context of accelerated aging, remain insufficiently studied. In this study, we employed an OEM mouse model and bulk RNA sequencing to investigate the underlying mechanisms. Our results show that OEM accelerates primordial follicle depletion and upregulates mTOR signaling pathway gene expression, along with mechanical stress and paracrine signaling via the Hippo and Myc pathways. OEM also induces irregular estrus and ovarian fibrosis in aging mice, decreases serum AMH levels, and increases FSH levels. Systemically, elevated serum IgG levels contribute to osteoporosis and cognitive decline, both linked to ovarian dysfunction and POF in OEM. These findings elucidate the mechanisms driving premature ovarian reserve depletion in OEM and highlight its broader systemic effects. This study emphasizes the importance of monitoring ovarian health and ectopic tissue to safeguard ovarian reserves and mitigate long-term risks such as osteoporosis and cognitive decline.

The prostaglandin E2 (PGE2) signaling has traditionally been viewed to play a pivotal role in endometriosis, linking inflammation and hyperestrogenism. We have previously reported that asectopic endometrium becomes more fibrotic, the expression of both COX-2 and PGE2 receptors (EP2 and EP4) are reduced. This study further investigatedwhether the expression levels of genes involved in the biosynthesis and metabolism of PGE2in ectopic endometrium diminish in concordance with increasing lesional fibrosis. We performed immunohistochemistry analyses of COX-2, mPGES-1, mPGES-2, cPGES, 15-PGDH, EP2 and EP4 and Masson trichrome staining for ovarian endometrioma (OE), adenomyosis (AD), and deep endometriosis (DE) tissue samples and control endometrial tissue samples (CT). Gene and protein expression analyses were performed by real-time RT-PCR and Western blotting, respectively. We found that as the extent of lesional fibrosis increased, immunoexpression of COX-2, mPGES-1/2, cPGES, EP2 and EP4 in OE lesions was increased but no change in these genes/proteins in DE lesions as compared with CT. Immunoexpression of COX-2 was found to be reduced while that of 15-PGDH was found to be elevated in DE lesions. In AD lesions, only EP2 and COX-2 were overexpressed. Thus, our data indicate that when the extent of lesional fibrosis is high, the PGE2 signaling pathway is depressed, manifesting as reduced COX-2 expression and elevated expression of 15-PGDH. They underscore the fact that not all ectopic endometria are the same and equal, and highlight the importance of the extracellular matrix in shaping the lesional behavior and response to drug treatment.

Our purpose is to explore the influence of Hua Yu Xiao Zheng (HYXZ) decoction on the senescence of ectopic endometrial stromal cells (ESCs) in endometriosis as well as its relevant mechanisms.

The proliferation, apoptosis, migration, and invasion of primary ectopic ESCs was assessed utilizing EdU assay, flow cytometry, and transwell assays. Moreover, the effects of HYXZ decoction on oxidative stress were evaluated using DCFH-DA probe and via measuring MDA, GSH, SOD and GPx levels. The function of HYXZ decoction on cell senescence were explored through utilizing SA-β-gal staining and measuring the cumulative population doubling level and the average telomere length. The protein expression was measured using western blotting analysis. Endometriosis in rats was surgically induced, and the efficacy and mechanism of HYXZ decoction were determined in vivo.

HYXZ decoction inhibited the growth, migration, and invasion of ectopic ESCs, but induced oxidative stress and senescence. HYXZ decoction inhibited PI3K/AKT signaling in ectopic ESCs. PI3K-AKT signaling pathway activator (740Y-P) significantly reversed the inhibitory effects of HYXZ decoction on ectopic ESCs. In rats with endometriosis, oral administration of HYXZ decoction inhibited lesion volume alone with the increased oxidative stress and cell senescence, as well as the decreased PI3K/AKT activity.

HYXZ decoction might repress the growth and migration of ectopic ESCs, and induce oxidative stress and senescence through suppressing PI3K/AKT signaling. This finding indicates that HYXZ decoction may be a potential therapeutic drug against endometriosis.

Our aim was to review the evidence concerning the noninvasive diagnosis of endometriosis in adolescents.

A systematic review was written following the SWiM reporting guidelines. The study research was made across three databases (MEDLINE/PubMed, Scopus, and Web of Science) to identify articles about the adolescent population and the diagnosis of endometriosis through noninvasive methods. The search included the keywords "endometriosis," "adolescents," "diagnosis," "ultrasound," and "MRI." Only English-language articles were considered, and those published prior to 2000 were excluded. The established outcomes focused on clinical symptoms, ultrasound (US), and magnetic resonance imaging (MRI) findings suggestive of endometriosis.

We included 26 articles, mostly comprising case series and cross-sectional studies. The pooled analysis involved 2,299 female adolescents (age range 8-25 years old) with clinically suspected, imaged, and/or surgically confirmed endometriosis. The most frequently reported symptom was dysmenorrhea, followed by chronic pelvic pain. Among adolescents clinically suspected of endometriosis undergoing ultrasound (US), 32.8% exhibited at least one sign of endometriosis. Of the 167 patients with ultrasound-diagnosed endometriosis, 48.5% had deep infiltrating endometriosis (DIE), and 45.5% had an endometrioma detected. Three studies assessed MRI findings, revealing that 49.8% presented with signs of endometriosis.

Dysmenorrhea and chronic pelvic pain stand out as key symptoms of adolescent endometriosis. Although their diagnostic accuracy varies, US and MRI have emerged as valuable tools for diagnosing the disease. While the US may have limitations, especially in detecting subtle lesions, MRI shows promise, even in cases with normal previous ultrasounds. Early recognition and proactive diagnosis are crucial for improving the management of endometriosis in adolescents.

To investigate the underlying mechanisms driving the opposing effects of transforming growth factor-beta 1 (TGFβ1) on the proliferation of control (CESCs) and ectopic (EESCs) endometrial stromal cells.

Cell proliferation assays (CCK-8 and colony formation) were employed to assess the effects of TGFβ1 on CESC and EESC proliferation. An immortalized human endometrial stromal cell line (HESC) was used to elucidate the mechanisms behind cytostatic effect of TGFβ1 and the potential role of cyclooxygenase (COX)-2 in mediating the modulation of TGFβ1 signaling.

This study demonstrated that TGFβ1 inhibited the proliferation of CESCs and HESCs while significantly promoting the proliferation of EESCs. In both CESCs and HESCs, TGFβ1-induced growth arrest was primarily mediated by cell cycle arrest rather than apoptosis. Mechanistically, TGFβ1 activated both Smad3 and ERK1/2 signaling pathways, with Smad3 acting to inhibit proliferation and ERK1/2 to promote it. Notably, overexpression of COX-2 in HESCs abolished the cytostatic effect of TGFβ1 by enhancing ERK1/2 signaling and decreasing Smad3 protein levels and its nuclear translocation. Similar effects were observed following prostaglandin E2 (PGE2) treatment. In contrast, inhibition of COX-2 activity in EESCs resulted in increased Smad3 expression, reduced ERK1/2 activation, and a restoration of the cytostatic effect of TGFβ1.

COX-2 modulates the effects of TGFβ1 on endometrial stromal cells by altering the balance between the Smad3 and ERK1/2 signaling pathways, thereby converting TGFβ1 from a growth inhibitor to a proliferation stimulator.

Endometriosis is characterized by a range of non-specific symptoms which may contribute to the significant delay in diagnosis. Knowledge about the distribution of endometriosis symptoms across different geographical regions as well as other sociodemographic factors could add knowledge and guide initiatives to reduce this underdiagnosis. This study aims to explore how the prevalence of endometriosis symptoms and indicators are linked to the different sociodemographic factors.

The study used data from the CYKLUS-survey; a women's health survey sent to 63,199 Danish women aged 16 to 51 in 2023. Self-reported information on endometriosis symptoms and indicators was linked to Danish register data on sociodemographic factors. Age-standardized prevalence of six endometriosis symptoms and indicators were estimated for each of the nine different regions of residence and for the whole country. In addition, logistic regression analysis was used to estimate the association between sociodemographic factors and the six endometriosis symptoms and indicators.

11,407 women were included in the study. Age-standardized prevalence of symptoms showed little variation across Danish regions. However, younger age, lower socioeconomic status, and non-Danish origin were found to be associated with higher prevalences, and higher education was found to be associated with lower prevalences.

No major regional differences in endometriosis symptoms and indicators were found. However, associations were found between several sociodemographic factors and endometriosis symptoms and indicators, suggesting disparities in the burden of symptoms. These findings call for further investigation into factors causing these disparities in Denmark.

Ovarian endometrioma (OEM), a particularly severe form of endometriosis, is an oestrogen-dependent condition often associated with pain and infertility. The mechanisms by which OEM impairs fertility, particularly through its direct impact on oocyte-cumulus cell (CC) communication and related pathways, remain poorly understood. This study investigates the impact of OEM on oocyte-CC communication and explores melatonin's therapeutic potential. We used a mouse model of OEM and employed ovarian transcriptome and gene set enrichment analyses to identify disrupted gene pathways, alongside phalloidin staining for cytoskeletal analysis, gap junction coupling analysis for intercellular communication, and mitochondrial function assessments for cellular metabolism. Our results showed that OEM significantly impairs steroidogenesis and cumulus cell function, leading to increased apoptosis, disrupted transzonal projections (TZPs), and impaired antioxidant transfer to oocytes. This culminates in oxidative stress, mitochondrial dysfunction, and compromised ATP production. OEM oocytes also exhibited severe abnormalities, including DNA damage, maturation defects, spindle assembly disruptions, and increased aneuploidy. This study identifies disrupted TZPs as a key pathological feature in OEM and highlights melatonin's potential to restore intercellular communication, mitigate oxidative damage, and improve reproductive outcomes.

Endometriosis affects about 10 % of women of reproductive age, leading to a disabling gynecologic condition. Chronic pain, inflammation, and oxidative stress have been identified as the molecular pathways involved in the progression of this disease, although its precise etiology remains uncertain. Although mitochondria are considered crucial organelles for cellular activity, their dysfunction has been linked to the development of this disease. The purpose of this review is to examine the functioning of the mitochondrion in endometriosis: in particular, we focused on the mitochondrial dynamics of biogenesis, fusion, and fission. Since excessive mitochondrial activity is reported to affect cell proliferation, we also considered mitophagy as a mechanism involved in limiting disease development. To better understand mitochondrial activity, we also considered alterations in circadian rhythms, the gut microbiome, and estrogen receptors: indeed, these mechanisms are also involved in the development of endometriosis. In addition, we focused on recent research about the impact of numerous substances on mitochondrial activity; some of them may offer a future breakthrough in endometriosis treatment by acting on mitochondria and inhibiting cell proliferation.

Endometriosis is an inflammatory disease, involving immune cell infiltration and production of inflammatory mediators. Ferroptosis has recently been recognized as a mode of controlled cell death and the iron overload and peroxidative environment prevailing in the ectopic endometrium facilitates the occurrence of ferroptosis. In the current investigation, gene expression data was obtained from the dataset GSE7305.The variation in infiltration of immune cells amongst the samples with endometriosis and normal tissue was analysed using the CIBERSORTx tool which revealed higher infiltration of T cells gamma delta, macrophages M2, B cells naïve, T cells CD4 memory resting cells, plasma cells, T cells CD8 and mast cells activated in the tissue samples with endometriosis. An overlap of the differentially expressed genes (DEGs) and ferroptosis related genes revealed 32 ferroptosis related DEGs (FR-DEGs). GO and KEGG pathway analysis showed the FR-DEGs to be enriched in ferroptosis. The PPI network of the FR-DEGs was constructed and TP53, HMOX1, CAV1, CDKN1A, CD44, EPAS1, SLC2A1, MAP3K5, GCLC and FANCD2 were identified as the hub genes. Pearson correlation revealed significant correlation between the hub genes and infiltrating immune cells in endometriosis, thereby suggesting existence of a regulatory crosstalk between immune responses and ferroptosis in endometriosis. Hub gene- miRNA network analysis revealed that 7 of the 10 hub genes were targets of 3 miRNAs -hsa-miR-20a-5p, hsa-miR-16-5p and hsa-miR-17-5p, thereby providing further insight into the regulatory mechanisms underlying disease progression. Predictive analysis and cross validation studies revealed TP53 and CDKN1A as common targets of hsa-miR-16-5p, hsa-miR-17-5p, and hsa-miR-20a-5p, thereby revealing their regulatory roles in ferroptosis and immune modulatory pathways relevant to endometriosis. The present study indicates an important role of both immune dysregulation and ferroptosis in the pathogenesis of endometriosis and identifies ferroptosis related hub genes and their miRNA regulators as favourable novel targets for further studies and therapeutic interventions.

A considerable number of women of reproductive age suffer from endometriosis worldwide. There is a significant physical, mental, and financial burden on patients affected by this condition in terms of pelvic pain, either continuously or intermittently, dysmenorrhea, infertility, and a higher risk of certain types of cancer. Several treatments available in clinical settings for endometriosis management do not provide adequate efficacy and have undesirable side effects. Transcription factors (TFs) are crucial regulators of key biological processes involved in endometriosis. Here, we elaborated on the research progress regarding the crucial roles of TFs in endometriosis, emphasizing their implications for clinical outcomes and critical therapeutic contributions. By delving into their involvement in key processes, such as cell proliferation and apoptosis, we revealed the multifaceted role of key TFs in disease progression. We aimed to provide a systemic understanding of TFs regulation in endometriosis pathogenesis, establishing a foundation for innovative treatment approaches.

Endometriosis is a female-specific chronic condition that affects 1 in 10 women and other individuals with a uterus worldwide with common symptoms that include pelvic pain and infertility. Reliable and effective non-invasive biomarkers for endometriosis do not exist, and therefore currently a diagnosis of endometriosis requires direct visualization of lesions at surgery. Similarly, few safe and effective management strategies exist for endometriosis, with hormonal interventions and surgery only providing temporary symptom control. The development of endometriosis involves the implantation and proliferation of ectopic endometrial cells which triggers local and systemic inflammation and fibrosis. While multiple genetic, environmental, and lifestyle factors appear to influence the natural history of endometriosis, chronic inflammation is a hallmark feature associated with development and progression of the disease. Data further shows that endometriosis commonly co-occurs with autoimmune diseases, adding evidence that immune dysfunction likely contributes to the pathogenesis of this disorder. Specific innate and adaptive immune system drivers of endometriosis remain to be identified and additional research is needed to elucidate the mechanistic underpinnings of this debilitating disease. In this narrative review, we discuss the shared biological mechanisms and plausible immune-related connections between endometriosis and autoimmunity.