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Chen H, Chen Q, Wang D, Lv M, Wang L, Chen Y, Xi F, Huang H, Luo Q. The mediating effect of maternal blood lipids on the association between maternal exposure to PM 2.5 and birth weight: a retrospective birth cohort study in Zhejiang, China. Lipids Health Dis 2025; 24:193. [PMID: 40426116 DOI: 10.1186/s12944-025-02614-6] [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: 02/06/2025] [Accepted: 05/17/2025] [Indexed: 05/29/2025] Open
Abstract
BACKGROUND Maternal PM2.5 exposure and lipid levels during pregnancy were independently detected associated with birth weight. Potential mediating factors still remain unclear. METHODS This study aimed to examine the association of maternal PM2.5 exposure and birth weight, and explore the potential mediation effect of maternal blood lipids in the relationship between PM2.5 exposure and birth weight. 5,162 pregnant women from Zhejiang, China were included in the study during 2013-2014. We measured blood lipids for each participant in the second and third trimesters. Air pollution exposure in residential districts was estimated based on satellite data for each individual throughout three trimesters in pregnancy. Linear mixed-effects models were employed to examine associations between PM2.5 and birth weight. Using a mediation analysis approach, we decomposed the total effect of PM2.5 on birth weight into natural direct and indirect effects via blood lipid concentration. RESULTS After adjusting for covariates, a 10 µg/m3 increment in PM2.5 during the second trimester was directly associated with an 11.65 g increase in birth weight (95% CI: 2.99, 20.31 g). The indirect effects of PM2.5 exposure (each 10 µg/m3 increase) on birth weight, mediated through elevated maternal lipid levels, were - 2.35 g (95% CI: -4.07, -0.63 g) for total cholesterol to high-density lipoprotein cholesterol ratio (TC: HDL ratio), -0.69 g (95% CI: -1.16, -0.22 g) for Triglycerides (TG), and - 1.80 g (95% CI: -3.19, -0.41 g) for HDL-C, during the second trimester. CONCLUSIONS Findings suggest prenatal PM2.5 exposure may impact term birth weight via direct biological effects and lipid-mediated pathways, underscoring the importance of incorporating air pollution mitigation into perinatal care and advancing biomarker-driven fetal monitoring. Future research should clarify PM2.5 component-specific effects, decode placental-fetal lipid regulatory mechanisms, and validate pollution-metabolism-outcome relationships through multi-regional cohorts to inform precision environmental health interventions and clinical risk management.
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Affiliation(s)
- Huiqi Chen
- Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK
- Department of Obstetrics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Qinqing Chen
- Department of Obstetrics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Danxiao Wang
- Cixi People's Hospital Medical and Health Group, Cixi People's Hospital, Cixi, 315300, China
| | - Min Lv
- Department of Obstetrics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Liyun Wang
- School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
| | - Yuan Chen
- Department of Obstetrics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Fangfang Xi
- Department of Obstetrics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Hefeng Huang
- Key Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
| | - Qiong Luo
- Key Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
- Zhejiang Provincial Birth Defect Control and Prevention Research Center, Hangzhou, 310006, China.
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Joshi N, Joshi S. Fatty acid metabolism in the placentae of gestational diabetes mellitus. Prostaglandins Leukot Essent Fatty Acids 2025; 205:102682. [PMID: 40209642 DOI: 10.1016/j.plefa.2025.102682] [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: 01/25/2025] [Revised: 04/04/2025] [Accepted: 04/04/2025] [Indexed: 04/12/2025]
Abstract
The prevalence of gestational diabetes mellitus (GDM), a metabolic complication during pregnancy is increasing rapidly. It exerts various short and long term effects on the mother and the child. Nonetheless, the mechanisms underlying the pathophysiology of GDM are still not clear. Placenta is a key 'programming' agent and any impairment in placental structure and function may hamper the fetal growth and development. Omega-3 and omega-6 fatty acids are key nutrients involved in placental and fetal development. The fatty acids transport from maternal circulation towards the fetus depends on the fatty acid status of the mother, fatty acid metabolism of the placenta and placental transport of fatty acids. Alteration in any of these could influence the fatty acids transport towards the fetus thereby affecting the fetal brain development and leading to impairment in cognitive function in the off-spring. We propose a role for placental fatty acid metabolism in influencing fetal growth and development which in turn can have an impact on cognitive development of the offspring born to GDM women.
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Affiliation(s)
- Nikita Joshi
- Mother and Child Health, ICMR-Collaborating Centre of Excellence (ICMR-CCoE), Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune, India
| | - Sadhana Joshi
- Mother and Child Health, ICMR-Collaborating Centre of Excellence (ICMR-CCoE), Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune, India.
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Massalha M, Iskander R, Hassan H, Spiegel E, Erez O, Nachum Z. Gestational diabetes mellitus - more than the eye can see - a warning sign for future maternal health with transgenerational impact. FRONTIERS IN CLINICAL DIABETES AND HEALTHCARE 2025; 6:1527076. [PMID: 40235646 PMCID: PMC11997571 DOI: 10.3389/fcdhc.2025.1527076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Accepted: 02/06/2025] [Indexed: 04/17/2025]
Abstract
Gestational diabetes mellitus (GDM) is regarded by many as maternal maladaptation to physiological insulin resistance during the second half of pregnancy. However, recent evidence indicates that alterations in carbohydrate metabolism can already be detected in early pregnancy. This observation, the increasing prevalence of GDM, and the significant short and long-term implications for the mother and offspring call for reevaluation of the conceptual paradigm of GDM as a syndrome. This review will present evidence for the syndromic nature of GDM and the controversies regarding screening, diagnosis, management, and treatment.
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Affiliation(s)
- Manal Massalha
- Department of Obstetrics and Gynecology, Emek Medical Center, Afula, Israel
- Rappaport Faculty of Medicine, Technion, Institute of technology, Haifa, Israel
| | - Rula Iskander
- Department of Obstetrics and Gynecology, Emek Medical Center, Afula, Israel
| | - Haya Hassan
- Department of Obstetrics and Gynecology, Emek Medical Center, Afula, Israel
| | - Etty Spiegel
- Department of Obstetrics and Gynecology, Emek Medical Center, Afula, Israel
| | - Offer Erez
- Department of Obstetrics and Gynecology, Soroka University Medical Center, Beer Sheva, Israel
- Faculty of Medicine, Ben Gurion University of the Negev, Beer Sheva, Israel
- Department of Obstetrics and Gynecology, Hutzel Women’s Hospital, Wayne State University, Detroit, MI, United States
| | - Zohar Nachum
- Department of Obstetrics and Gynecology, Emek Medical Center, Afula, Israel
- Rappaport Faculty of Medicine, Technion, Institute of technology, Haifa, Israel
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4
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Wu B, Gao A, He B, Chen Y, Kong X, Wen F, Gao H. RNA-seq analysis of mitochondria-related genes regulated by AMPK in the human trophoblast cell line BeWo. Animal Model Exp Med 2025; 8:649-661. [PMID: 39445545 PMCID: PMC12008445 DOI: 10.1002/ame2.12475] [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: 04/27/2024] [Accepted: 07/11/2024] [Indexed: 10/25/2024] Open
Abstract
BACKGROUND How AMP activated protein kinase (AMPK) signaling regulates mitochondrial functions and mitophagy in human trophoblast cells remains unclear. This study was designed to investigate potential players mediating the regulation of AMPK on mitochondrial functions and mitophagy by next generation RNA-seq. METHODS We compared ATP production in protein kinase AMP-activated catalytic subunit alpha 1/2 (PRKAA1/2) knockdown (AKD) and control BeWo cells using the Seahorse real-time ATP rate test, then analyzed gene expression profiling by RNA-seq. Differentially expressed genes (DEG) were examined by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Then protein-protein interactions (PPI) among mitochondria related genes were further analyzed using Metascape and Ingenuity Pathway Analysis (IPA) software. RESULTS Both mitochondrial and glycolytic ATP production in AKD cells were lower than in the control BeWo cells (CT), with a greater reduction of mitochondrial ATP production. A total of 1092 DEGs were identified, with 405 upregulated and 687 downregulated. GO analysis identified 60 genes associated with the term 'mitochondrion' in the cellular component domain. PPI analysis identified three clusters of mitochondria related genes, including aldo-keto reductase family 1 member B10 and B15 (AKR1B10, AKR1B15), alanyl-tRNA synthetase 1 (AARS1), mitochondrial ribosomal protein S6 (MRPS6), mitochondrial calcium uniporter dominant negative subunit beta (MCUB) and dihydrolipoamide branched chain transacylase E2 (DBT). CONCLUSIONS In summary, this study identified multiple mitochondria related genes regulated by AMPK in BeWo cells, and among them, three clusters of genes may potentially contribute to altered mitochondrial functions in response to reduced AMPK signaling.
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Affiliation(s)
- Bin Wu
- Department of Reproductive MedicineCentral Hospital Affiliated to Shandong First Medical UniversityJinanShandongP.R. China
| | - Albert Gao
- Department of Physiology and Biophysics, College of MedicineHoward UniversityWashingtonDistrict of ColumbiaUSA
| | - Bin He
- Reproductive Physiology LaboratoryNational Research Institute for Family PlanningBeijingP.R. China
| | - Yun Chen
- Landmark BioWatertownMassachusettsUSA
| | - Xiangfeng Kong
- Institute of Subtropical Agriculture, Chinese Academy of SciencesChangshaHunanP.R. China
| | - Fayuan Wen
- Department of Biology, College of Arts and SciencesHoward UniversityWashingtonDistrict of ColumbiaUSA
| | - Haijun Gao
- Department of Physiology and Biophysics, College of MedicineHoward UniversityWashingtonDistrict of ColumbiaUSA
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Shamsad A, Gautam T, Singh R, Banerjee M. Genetic and epigenetic alterations associated with gestational diabetes mellitus and adverse neonatal outcomes. World J Clin Pediatr 2025; 14:99231. [DOI: 10.5409/wjcp.v14.i1.99231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 10/03/2024] [Accepted: 10/31/2024] [Indexed: 12/20/2024] Open
Abstract
Gestational diabetes mellitus (GDM) is a metabolic disorder, recognised during 24-28 weeks of pregnancy. GDM is linked with adverse newborn outcomes such as macrosomia, premature delivery, metabolic disorder, cardiovascular, and neurological disorders. Recent investigations have focused on the correlation of genetic factors such as β-cell function and insulin secretary genes (transcription factor 7 like 2, potassium voltage-gated channel subfamily q member 1, adiponectin etc.) on maternal metabolism during gestation leading to GDM. Epigenetic alterations like DNA methylation, histone modification, and miRNA expression can influence gene expression and play a dominant role in feto-maternal metabolic pathways. Interactions between genes and environment, resulting in differential gene expression patterns may lead to GDM. Researchers suggested that GDM women are more susceptible to insulin resistance, which alters intrauterine surroundings, resulting hyperglycemia and hyperinsulinemia. Epigenetic modifications in genes affecting neuroendocrine activities, and metabolism, increase the risk of obesity and type 2 diabetes in offspring. There is currently no treatment or effective preventive method for GDM, since the molecular processes of insulin resistance are not well understood. The present review was undertaken to understand the pathophysiology of GDM and its effects on adverse neonatal outcomes. In addition, the study of genetic and epigenetic alterations will provide lead to researchers in the search for predictive molecular biomarkers.
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Affiliation(s)
- Amreen Shamsad
- Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, Uttar Pradesh, India
| | - Tanu Gautam
- Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, Uttar Pradesh, India
| | - Renu Singh
- Department of Obstetrics and Gynecology, King George’s Medical University, Lucknow 226003, Uttar Pradesh, India
| | - Monisha Banerjee
- Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, Uttar Pradesh, India
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Khiat N, Girouard J, Kana Tsapi ES, Vaillancourt C, Van Themsche C, Reyes-Moreno C. TGFβ1 Restores Energy Homeostasis of Human Trophoblast Cells Under Hyperglycemia In Vitro by Inducing PPARγ Expression, AMPK Activation, and HIF1α Degradation. Cells 2025; 14:45. [PMID: 39791746 PMCID: PMC11720224 DOI: 10.3390/cells14010045] [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: 11/12/2024] [Revised: 12/23/2024] [Accepted: 01/01/2025] [Indexed: 01/12/2025] Open
Abstract
Elevated glucose levels at the fetal-maternal interface are associated with placental trophoblast dysfunction and increased incidence of pregnancy complications. Trophoblast cells predominantly utilize glucose as an energy source, metabolizing it through glycolysis in the cytoplasm and oxidative respiration in the mitochondria to produce ATP. The TGFβ1/SMAD2 signaling pathway and the transcription factors PPARγ, HIF1α, and AMPK are key regulators of cell metabolism and are known to play critical roles in extravillous trophoblast cell differentiation and function. While HIF1α promotes glycolysis over mitochondrial respiration, PPARγ and AMPK encourage the opposite. However, the interplay between TGFβ1 and these energy-sensing regulators in trophoblast cell glucose metabolism remains unclear. This study aimed to investigate whether and how TGFβ1 regulates energy metabolism in trophoblast cells exposed to normal and high glucose conditions. The trophoblast JEG-3 cells were incubated in normal (5 mM) and high (25 mM) glucose conditions for 24 h in the absence and the presence of TGFβ1. The protein expression levels of phosphor (p)-SMAD2, GLUT1/3, HIF1α, PPARγ, p-AMPK, and specific OXPHOS protein subunits were determined by western blotting, and ATP and lactate production by bioluminescent assay kits. JEG-3 cells exposed to 25 mM glucose decreased ATP production but did not affect lactate production. These changes led to a reduction in the expression levels of GLUT1/3, mitochondrial respiratory chain proteins, and PPARγ, coinciding with an increase in HIF1α expression. Conversely, TGFβ1 treatment at 25 mM glucose reduced HIF1α expression while enhancing the expression levels of GLUT1/3, PPARγ, p-AMPK, and mitochondrial respiratory chain proteins, thereby rejuvenating ATP production. Our findings reveal that high glucose conditions disrupt cellular glucose metabolism in trophoblast cells by perturbing mitochondrial oxidative respiration and decreasing ATP production. Treatment with TGFβ1 appears to counteract this trend, probably by enhancing both glycolytic and mitochondrial metabolism, suggesting a potential regulatory role of TGFβ1 in placental trophoblast cell glucose metabolism.
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Affiliation(s)
- Nihad Khiat
- Groupe de Recherche en Signalisation Cellulaire (GRSC), Département de Biologie Médicale, Université du Québec à Trois-Rivières, 3351 Boulevard des Forges, Trois-Rivières, QC G8Z 4M3, Canada; (N.K.); (J.G.); (E.S.K.T.); (C.V.T.)
- Centre de Recherche Interuniversitaire en Reproduction et Développement-Réseau Québécois en Reproduction (CIRD-RQR), Université de Montréal, St-Hyacinthe, QC J2S 2M2, Canada;
- Regroupement Intersectoriel de Recherche en Santé de l’Université du Québec (RISUQ), Université du Québec, Québec, QC G1K 9H7, Canada
| | - Julie Girouard
- Groupe de Recherche en Signalisation Cellulaire (GRSC), Département de Biologie Médicale, Université du Québec à Trois-Rivières, 3351 Boulevard des Forges, Trois-Rivières, QC G8Z 4M3, Canada; (N.K.); (J.G.); (E.S.K.T.); (C.V.T.)
- Centre de Recherche Interuniversitaire en Reproduction et Développement-Réseau Québécois en Reproduction (CIRD-RQR), Université de Montréal, St-Hyacinthe, QC J2S 2M2, Canada;
- Regroupement Intersectoriel de Recherche en Santé de l’Université du Québec (RISUQ), Université du Québec, Québec, QC G1K 9H7, Canada
| | - Emmanuelle Stella Kana Tsapi
- Groupe de Recherche en Signalisation Cellulaire (GRSC), Département de Biologie Médicale, Université du Québec à Trois-Rivières, 3351 Boulevard des Forges, Trois-Rivières, QC G8Z 4M3, Canada; (N.K.); (J.G.); (E.S.K.T.); (C.V.T.)
- Centre de Recherche Interuniversitaire en Reproduction et Développement-Réseau Québécois en Reproduction (CIRD-RQR), Université de Montréal, St-Hyacinthe, QC J2S 2M2, Canada;
- Regroupement Intersectoriel de Recherche en Santé de l’Université du Québec (RISUQ), Université du Québec, Québec, QC G1K 9H7, Canada
| | - Cathy Vaillancourt
- Centre de Recherche Interuniversitaire en Reproduction et Développement-Réseau Québécois en Reproduction (CIRD-RQR), Université de Montréal, St-Hyacinthe, QC J2S 2M2, Canada;
- Regroupement Intersectoriel de Recherche en Santé de l’Université du Québec (RISUQ), Université du Québec, Québec, QC G1K 9H7, Canada
- Institut National de la Recherche Scientifique (INRS)-Centre Armand Frappier Santé Biotechnologie and Research Centre CIUSSS-Nord-de-l’île-de-Montréal, Laval, QC H7V 1B7, Canada
| | - Céline Van Themsche
- Groupe de Recherche en Signalisation Cellulaire (GRSC), Département de Biologie Médicale, Université du Québec à Trois-Rivières, 3351 Boulevard des Forges, Trois-Rivières, QC G8Z 4M3, Canada; (N.K.); (J.G.); (E.S.K.T.); (C.V.T.)
- Centre de Recherche Interuniversitaire en Reproduction et Développement-Réseau Québécois en Reproduction (CIRD-RQR), Université de Montréal, St-Hyacinthe, QC J2S 2M2, Canada;
- Regroupement Intersectoriel de Recherche en Santé de l’Université du Québec (RISUQ), Université du Québec, Québec, QC G1K 9H7, Canada
| | - Carlos Reyes-Moreno
- Groupe de Recherche en Signalisation Cellulaire (GRSC), Département de Biologie Médicale, Université du Québec à Trois-Rivières, 3351 Boulevard des Forges, Trois-Rivières, QC G8Z 4M3, Canada; (N.K.); (J.G.); (E.S.K.T.); (C.V.T.)
- Centre de Recherche Interuniversitaire en Reproduction et Développement-Réseau Québécois en Reproduction (CIRD-RQR), Université de Montréal, St-Hyacinthe, QC J2S 2M2, Canada;
- Regroupement Intersectoriel de Recherche en Santé de l’Université du Québec (RISUQ), Université du Québec, Québec, QC G1K 9H7, Canada
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Moreli JB, Ferrari N, Ruocco AMC, Santos MGDO, Lorenzon AR, Carlos CP, Rudge MVC, Calderon IDMP. Influence of maternal hyperglycemia on placental capillary distribution. EINSTEIN-SAO PAULO 2024; 22:eAO0583. [PMID: 39504088 PMCID: PMC11634342 DOI: 10.31744/einstein_journal/2024ao0583] [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: 05/17/2023] [Accepted: 02/21/2024] [Indexed: 11/08/2024] Open
Abstract
OBJECTIVE This study was conducted to investigate the distribution of placental villous vessels in pregnant women with different degrees of hyperglycemia. METHODS A cross-sectional study was performed using placental samples from 30 pregnant women without diabetes (n=10), with gestational diabetes mellitus (n=10), and with previous diabetes (type 1 and type 2 diabetes; n=10). Maternal glycemic control was evaluated using the glycemic mean and glycated hemoglobin levels. Placental samples were obtained during elective cesarean sections and processed for villous vessel analysis using immunohistochemistry for Von Willebrand factor. Vessels within 10μm of the villus margin were classified as peripheral, and vessels at a distance greater than 10μm were classified as central. The number, area, and perimeter of all vessels were evaluated, and the relationship between vessel area and total area of placental villus was calculated. RESULTS Pregnant women with gestational diabetes mellitus and those with previous diabetes had higher glycated hemoglobin levels. The number of vessels was reduced in the villi of the previous Diabetes Group owing to peripheral reduction. Additionally, the area, perimeter, and percentage of peripheral blood were lower in the previous Diabetes Group than in the Non-Diabetic Group. CONCLUSION Maternal glycemic levels can modify placental capillary distribution.
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Affiliation(s)
- Jusciele Brogin Moreli
- Universidade Estadual Paulista "Júlio de Mesquita FilhoFaculdade de Medicina de BotucatuDepartment of Gynecology and ObstetricsBotucatuSPBrazilDepartment of Gynecology and Obstetrics, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista "Júlio de Mesquita Filho, Botucatu, SP, Brazil.
- Faculdade de Medicina de São José do Rio PretoFaculdade CeresSão José do Rio PretoSPBrazilFaculdade Ceres - Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, SP, Brazil.
| | - Natália Ferrari
- Faculdade de Medicina de São José do Rio PretoFaculdade CeresSão José do Rio PretoSPBrazilFaculdade Ceres - Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, SP, Brazil.
| | - Ana Maria Cirino Ruocco
- Universidade Estadual Paulista "Júlio de Mesquita FilhoFaculdade de Medicina de BotucatuDepartment of Gynecology and ObstetricsBotucatuSPBrazilDepartment of Gynecology and Obstetrics, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista "Júlio de Mesquita Filho, Botucatu, SP, Brazil.
| | - Mariana Gomes de Oliveira Santos
- Faculdade de Medicina de São José do Rio PretoFaculdade CeresSão José do Rio PretoSPBrazilFaculdade Ceres - Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, SP, Brazil.
| | - Aline Rodrigues Lorenzon
- Huntington Medicina Reprodutiva-Eugin GroupSão PauloSPBrazilHuntington Medicina Reprodutiva-Eugin Group, São Paulo, SP, Brazil.
| | - Carla Patrícia Carlos
- Huntington Medicina Reprodutiva-Eugin GroupSão PauloSPBrazilHuntington Medicina Reprodutiva-Eugin Group, São Paulo, SP, Brazil.
| | - Marilza Vieira Cunha Rudge
- Universidade Estadual Paulista "Júlio de Mesquita FilhoFaculdade de Medicina de BotucatuDepartment of Gynecology and ObstetricsBotucatuSPBrazilDepartment of Gynecology and Obstetrics, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista "Júlio de Mesquita Filho, Botucatu, SP, Brazil.
| | - Iracema de Mattos Paranhos Calderon
- Universidade Estadual Paulista "Júlio de Mesquita FilhoFaculdade de Medicina de BotucatuDepartment of Gynecology and ObstetricsBotucatuSPBrazilDepartment of Gynecology and Obstetrics, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista "Júlio de Mesquita Filho, Botucatu, SP, Brazil.
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Lin J, Zhao D, Liang Y, Liang Z, Wang M, Tang X, Zhuang H, Wang H, Yin X, Huang Y, Yin L, Shen L. Proteomic analysis of plasma total exosomes and placenta-derived exosomes in patients with gestational diabetes mellitus in the first and second trimesters. BMC Pregnancy Childbirth 2024; 24:713. [PMID: 39478498 PMCID: PMC11523606 DOI: 10.1186/s12884-024-06919-9] [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: 08/20/2024] [Accepted: 10/22/2024] [Indexed: 11/03/2024] Open
Abstract
Gestational diabetes mellitus (GDM) is the first spontaneous hyperglycemia during pregnancy. Early diagnosis and intervention are important for the management of the disease. This study compared and analyzed the proteins of total plasma exosomes (T-EXO) and placental-derived exosomes (PLAP-EXO) in pregnant women who subsequently developed GDM (12-16 weeks), GDM patients (24-28 weeks) and their corresponding controls to investigate the pathogenesis and biomarkers of GDM associated with exosomes. The exosomal proteins were extracted and studied by proteomics approach, then bioinformatics analysis was applied to the differentially expressed proteins (DEPs) between the groups. At 12-16 and 24-28 weeks of gestation, 36 and 21 DEPs were identified in T-EXO, while 34 and 20 DEPs were identified in PLAP-EXO between GDM and controls, respectively. These proteins are mainly involved in complement pathways, immunity, inflammation, coagulation and other pathways, most of them have been previously reported as blood or exosomal proteins associated with GDM. The findings suggest that the development of GDM is a progressive process and that early changes promote the development of the disease. Maternal and placental factors play a key role in the pathogenesis of GDM. These proteins especially Hub proteins have the potential to become predictive and diagnostic biomarkers for GDM.
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Affiliation(s)
- Jing Lin
- College of Life Science and Oceanography, Shenzhen University, Shenzhen, 518071, P. R. China
| | - Danqing Zhao
- Department of Obstetrics and Gynecology, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, P. R. China
| | - Yi Liang
- Department of Clinical Nutrition, Affiliated Hospital of Guizhou Medical University, Guiyang, P.R. China
| | - Zhiyuan Liang
- College of Life Science and Oceanography, Shenzhen University, Shenzhen, 518071, P. R. China
| | - Mingxian Wang
- College of Life Science and Oceanography, Shenzhen University, Shenzhen, 518071, P. R. China
| | - Xiaoxiao Tang
- College of Life Science and Oceanography, Shenzhen University, Shenzhen, 518071, P. R. China
| | - Hongbin Zhuang
- College of Life Science and Oceanography, Shenzhen University, Shenzhen, 518071, P. R. China
| | - Hanghang Wang
- College of Life Science and Oceanography, Shenzhen University, Shenzhen, 518071, P. R. China
| | - Xiaoping Yin
- Department of Obstetrics and Gynecology, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, P. R. China
| | - Yuhan Huang
- College of Life Science and Oceanography, Shenzhen University, Shenzhen, 518071, P. R. China
| | - Li Yin
- Department of Obstetrics and Gynecology, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, P. R. China
| | - Liming Shen
- College of Life Science and Oceanography, Shenzhen University, Shenzhen, 518071, P. R. China.
- Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, P. R. China.
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Siemers KM, Joss-Moore LA, Baack ML. Gestational Diabetes-like Fuels Impair Mitochondrial Function and Long-Chain Fatty Acid Uptake in Human Trophoblasts. Int J Mol Sci 2024; 25:11534. [PMID: 39519087 PMCID: PMC11546831 DOI: 10.3390/ijms252111534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 10/17/2024] [Accepted: 10/22/2024] [Indexed: 11/16/2024] Open
Abstract
In the parent, gestational diabetes mellitus (GDM) causes both hyperglycemia and hyperlipidemia. Despite excess lipid availability, infants exposed to GDM are at risk for essential long-chain polyunsaturated fatty acid (LCPUFA) deficiency. Isotope studies have confirmed less LCPUFA transfer from the parent to the fetus, but how diabetic fuels impact placental fatty acid (FA) uptake and lipid droplet partitioning is not well-understood. We evaluated the effects of high glucose conditions, high lipid conditions, and their combination on trophoblast growth, viability, mitochondrial bioenergetics, BODIPY-labeled fatty acid (FA) uptake, and lipid droplet dynamics. The addition of four carbons or one double bond to FA acyl chains dramatically affected the uptake in both BeWo and primary isolated cytotrophoblasts (CTBs). The uptake was further impacted by media exposure. The combination-exposed trophoblasts had more mitochondrial protein (p = 0.01), but impaired maximal and spare respiratory capacities (p < 0.001 and p < 0.0001), as well as lower viability (p = 0.004), due to apoptosis. The combination-exposed trophoblasts had unimpaired uptake of BODIPY C12 but had significantly less whole-cell and lipid droplet uptake of BODIPY C16, with an altered lipid droplet count, area, and subcellular localization, whereas these differences were not seen with individual high glucose or lipid exposure. These findings bring us closer to understanding how GDM perturbs active FA transport to increase the risk of adverse outcomes from placental and neonatal lipid accumulation alongside LCPUFA deficiency.
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Affiliation(s)
- Kyle M. Siemers
- Sanford School of Medicine, University of South Dakota, 414 E. Clark Street, Vermillion, SD 57069, USA;
| | - Lisa A. Joss-Moore
- Department of Pediatrics, University of Utah, 295 Chipeta Way, 2N131, Salt Lake City, UT 84108, USA;
| | - Michelle L. Baack
- Department of Pediatrics, Division of Neonatology, Sanford School of Medicine, University of South Dakota, 1400 W. 22nd St., Sioux Falls, SD 57105, USA
- Environmental Influences on Health and Disease Group, Sanford Research, 2301 E. 60th St., Sioux Falls, SD 57104, USA
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10
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Hung SC, Chan TF, Chan HC, Wu CY, Chan ML, Jhuang JY, Tan JQ, Mei JB, Law SH, Ponnusamy VK, Chan HC, Ke LY. Lysophosphatidylcholine Impairs the Mitochondria Homeostasis Leading to Trophoblast Dysfunction in Gestational Diabetes Mellitus. Antioxidants (Basel) 2024; 13:1007. [PMID: 39199251 PMCID: PMC11351454 DOI: 10.3390/antiox13081007] [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: 07/05/2024] [Revised: 08/10/2024] [Accepted: 08/16/2024] [Indexed: 09/01/2024] Open
Abstract
Gestational diabetes mellitus (GDM) is a common pregnancy disorder associated with an increased risk of pre-eclampsia and macrosomia. Recent research has shown that the buildup of excess lipids within the placental trophoblast impairs mitochondrial function. However, the exact lipids that impact the placental trophoblast and the underlying mechanism remain unclear. GDM cases and healthy controls were recruited at Kaohsiung Medical University Hospital. The placenta and cord blood were taken during birth. Confocal and electron microscopy were utilized to examine the morphology of the placenta and mitochondria. We determined the lipid composition using liquid chromatography-mass spectrometry in data-independent analysis mode (LC/MSE). In vitro studies were carried out on choriocarcinoma cells (JEG3) to investigate the mechanism of trophoblast mitochondrial dysfunction. Results showed that the GDM placenta was distinguished by increased syncytial knots, chorangiosis, lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) overexpression, and mitochondrial dysfunction. Lysophosphatidylcholine (LPC) 16:0 was significantly elevated in the cord blood LDL of GDM patients. In vitro, we demonstrated that LPC dose-dependently disrupts mitochondrial function by increasing reactive oxygen species (ROS) levels and HIF-1α signaling. In conclusion, highly elevated LPC in cord blood plays a pivotal role in GDM, contributing to trophoblast impairment and pregnancy complications.
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Affiliation(s)
- Shao-Chi Hung
- Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; (S.-C.H.); (J.-Q.T.); (J.-B.M.); (S.-H.L.)
| | - Te-Fu Chan
- Graduate Institute of Medicine, College of Medicine & Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807378, Taiwan;
- Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung 807377, Taiwan
| | - Hsiu-Chuan Chan
- PhD Program in Life Science, College of Life Science, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; (H.-C.C.); (V.K.P.)
| | - Chia-Ying Wu
- The Master Program of AI Application in Health Industry, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 807378, Taiwan;
| | - Mei-Lin Chan
- Division of Thoracic Surgery, Department of Surgery, MacKay Memorial Hospital, MacKay Medical College, Taipei 104217, Taiwan;
- Department of Medicine, MacKay Medical College, New Taipei 252005, Taiwan;
| | - Jie-Yang Jhuang
- Department of Medicine, MacKay Medical College, New Taipei 252005, Taiwan;
- Department of Pathology, Mackay Memorial Hospital, Tamsui Branch, New Taipei 251404, Taiwan
| | - Ji-Qin Tan
- Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; (S.-C.H.); (J.-Q.T.); (J.-B.M.); (S.-H.L.)
| | - Jia-Bin Mei
- Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; (S.-C.H.); (J.-Q.T.); (J.-B.M.); (S.-H.L.)
| | - Shi-Hui Law
- Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; (S.-C.H.); (J.-Q.T.); (J.-B.M.); (S.-H.L.)
| | - Vinoth Kumar Ponnusamy
- PhD Program in Life Science, College of Life Science, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; (H.-C.C.); (V.K.P.)
- Department of Medicinal and Applied Chemistry & Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Hua-Chen Chan
- Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; (S.-C.H.); (J.-Q.T.); (J.-B.M.); (S.-H.L.)
- Department of Medical Laboratory Science, College of Medicine, I-Shou University, Kaohsiung 824005, Taiwan
| | - Liang-Yin Ke
- Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; (S.-C.H.); (J.-Q.T.); (J.-B.M.); (S.-H.L.)
- Graduate Institute of Medicine, College of Medicine & Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807378, Taiwan;
- Center for Lipid Biosciences, Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807377, Taiwan
- Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807377, Taiwan
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11
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Fan H, Tan Y. Lipid Droplet-Mitochondria Contacts in Health and Disease. Int J Mol Sci 2024; 25:6878. [PMID: 38999988 PMCID: PMC11240910 DOI: 10.3390/ijms25136878] [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: 05/15/2024] [Revised: 06/19/2024] [Accepted: 06/20/2024] [Indexed: 07/14/2024] Open
Abstract
The orchestration of cellular metabolism and redox balance is a complex, multifaceted process crucial for maintaining cellular homeostasis. Lipid droplets (LDs), once considered inert storage depots for neutral lipids, are now recognized as dynamic organelles critical in lipid metabolism and energy regulation. Mitochondria, the powerhouses of the cell, play a central role in energy production, metabolic pathways, and redox signaling. The physical and functional contacts between LDs and mitochondria facilitate a direct transfer of lipids, primarily fatty acids, which are crucial for mitochondrial β-oxidation, thus influencing energy homeostasis and cellular health. This review highlights recent advances in understanding the mechanisms governing LD-mitochondria interactions and their regulation, drawing attention to proteins and pathways that mediate these contacts. We discuss the physiological relevance of these interactions, emphasizing their role in maintaining energy and redox balance within cells, and how these processes are critical in response to metabolic demands and stress conditions. Furthermore, we explore the pathological implications of dysregulated LD-mitochondria interactions, particularly in the context of metabolic diseases such as obesity, diabetes, and non-alcoholic fatty liver disease, and their potential links to cardiovascular and neurodegenerative diseases. Conclusively, this review provides a comprehensive overview of the current understanding of LD-mitochondria interactions, underscoring their significance in cellular metabolism and suggesting future research directions that could unveil novel therapeutic targets for metabolic and degenerative diseases.
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Affiliation(s)
- Hongjun Fan
- Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, College of Life Sciences, Shandong Normal University, Jinan 250014, China
| | - Yanjie Tan
- Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, College of Life Sciences, Shandong Normal University, Jinan 250014, China
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12
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McElwain CJ, Musumeci A, Manna S, McCarthy FP, McCarthy CM. L-ergothioneine reduces mitochondrial-driven NLRP3 activation in gestational diabetes mellitus. J Reprod Immunol 2024; 161:104171. [PMID: 38029485 DOI: 10.1016/j.jri.2023.104171] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 11/20/2023] [Accepted: 11/20/2023] [Indexed: 12/01/2023]
Abstract
BACKGROUND Maternal hyperglycaemia has a significant impact on placental metabolism and mitochondrial function. The NLRP3 inflammasome is responsive to endogenous signals of mitochondrial dysfunction. We tested our hypothesis that mitochondrial dysfunction orchestrates activation of the NLRP3 inflammasome and contributes to inflammation in gestational diabetes mellitus (GDM). METHODS Fasting blood, omental and placental tissue were collected on the day of caesarean section from nulliparous women with normal glucose tolerant (NGT) (n = 30) and GDM (n = 27) pregnancies. Cell-free mitochondrial DNA (cf-mtDNA) copy number was quantified by real-time PCR. M1-like (CD14+CD86+CD206-) and M2-like (CD14+CD86+CD206+) macrophage populations were characterized by flow cytometry. Immunoblotting for protein expression of NLRP3, ASC and caspase-1 was performed in maternal BMI and age-matched tissue samples. IL-1β and IL-18 were measured by multiplex ELISA. Placental explants from GDM participants were cultured for 24 h with 1 mM L-ergothioneine (antioxidant) and 1 µM MCC950 (NLRP3 inhibitor). RESULTS Cf-mtDNA copy numbers were significantly higher in GDM compared to NGT participants (p = 0.002). Placental populations of CD14+ (p = 0.02) and CD14+CD86+CD206- (p = 0.03) macrophages produced significantly increased levels of mitochondrial superoxide in GDM compared to NGT participants. Placental production of IL-18 (p = 0.04) was significantly increased in GDM. This increase in placental IL-18 was attenuated by treatment with 1 µM MCC950 (p = 0.0005), and 1 mM L-ergothioneine (p = 0.007). CONCLUSION Placental inflammation is significantly increased in women with GDM. Furthermore, this increase may be initiated by elevated production of mitochondrial superoxide by macrophage subpopulations and orchestrated by the NLRP3 inflammasome. The mitochondrial antioxidant, L-ergothioneine, ameliorates NLRP3-induced placental inflammation in GDM, identifying a potential therapeutic role.
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Affiliation(s)
- Colm J McElwain
- Department of Pharmacology and Therapeutics, Western Gateway Building, University College Cork, Cork, Ireland
| | - Andrea Musumeci
- Department of Pharmacology and Therapeutics, Western Gateway Building, University College Cork, Cork, Ireland
| | - Samprikta Manna
- Department of Obstetrics and Gynaecology, Cork University Maternity Hospital, Cork, Ireland
| | - Fergus P McCarthy
- Department of Obstetrics and Gynaecology, Cork University Maternity Hospital, Cork, Ireland
| | - Cathal M McCarthy
- Department of Pharmacology and Therapeutics, Western Gateway Building, University College Cork, Cork, Ireland.
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13
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Xie YP, Lin S, Xie BY, Zhao HF. Recent progress in metabolic reprogramming in gestational diabetes mellitus: a review. Front Endocrinol (Lausanne) 2024; 14:1284160. [PMID: 38234430 PMCID: PMC10791831 DOI: 10.3389/fendo.2023.1284160] [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: 08/28/2023] [Accepted: 12/11/2023] [Indexed: 01/19/2024] Open
Abstract
Gestational diabetes mellitus is a prevalent metabolic disease that can impact the normal course of pregnancy and delivery, leading to adverse outcomes for both mother and child. Its pathogenesis is complex and involves various factors, such as insulin resistance and β-cell dysfunction. Metabolic reprogramming, which involves mitochondrial oxidative phosphorylation and glycolysis, is crucial for maintaining human metabolic balance and is involved in the pathogenesis and progression of gestational diabetes mellitus. However, research on the link and metabolic pathways between metabolic reprogramming and gestational diabetes mellitus is limited. Therefore, we reviewed the relationship between metabolic reprogramming and gestational diabetes mellitus to provide new therapeutic strategies for maternal health during pregnancy and reduce the risk of developing gestational diabetes mellitus.
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Affiliation(s)
- Ya-ping Xie
- Nursing Department, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
| | - Shu Lin
- Centre of Neurological and Metabolic Research, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
- Group of Neuroendocrinology, Garvan Institute of Medical Research, Sydney, NSW, Australia
| | - Bao-yuan Xie
- Nursing Department, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
| | - Hui-fen Zhao
- Nursing Department, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
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14
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Gou R, Zhang X. Glycolysis: A fork in the path of normal and pathological pregnancy. FASEB J 2023; 37:e23263. [PMID: 37889786 DOI: 10.1096/fj.202301230r] [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: 06/19/2023] [Revised: 09/17/2023] [Accepted: 10/04/2023] [Indexed: 10/29/2023]
Abstract
Glucose metabolism is vital to the survival of living organisms. Since the discovery of the Warburg effect in the 1920s, glycolysis has become a major research area in the field of metabolism. Glycolysis has been extensively studied in the field of cancer and is considered as a promising therapeutic target. However, research on the role of glycolysis in pregnancy is limited. Recent evidence suggests that blastocysts, trophoblasts, decidua, and tumors all acquire metabolic energy at specific stages in a highly similar manner. Glycolysis, carefully controlled throughout pregnancy, maintains a dynamic and coordinated state, so as to maintain the homeostasis of the maternal-fetal interface and ensure normal gestation. In the present review, we investigate metabolic remodeling and the selective propensity of the embryo and placenta for glycolysis. We then address dysregulated glycolysis that occurs in the cellular interactive network at the maternal-fetal interface in miscarriage, preeclampsia, fetal growth restriction, and gestational diabetes mellitus. We provide new insights into the field of maternal-fetal medicine from a metabolic perspective, thus revealing the mystery of human pregnancy.
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Affiliation(s)
- Rui Gou
- Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing, P.R. China
| | - Xiaohong Zhang
- Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing, P.R. China
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15
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Diniz MS, Magalhães CC, Tocantins C, Grilo LF, Teixeira J, Pereira SP. Nurturing through Nutrition: Exploring the Role of Antioxidants in Maternal Diet during Pregnancy to Mitigate Developmental Programming of Chronic Diseases. Nutrients 2023; 15:4623. [PMID: 37960276 PMCID: PMC10649237 DOI: 10.3390/nu15214623] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2023] [Revised: 10/27/2023] [Accepted: 10/27/2023] [Indexed: 11/15/2023] Open
Abstract
Chronic diseases represent one of the major causes of death worldwide. It has been suggested that pregnancy-related conditions, such as gestational diabetes mellitus (GDM), maternal obesity (MO), and intra-uterine growth restriction (IUGR) induce an adverse intrauterine environment, increasing the offspring's predisposition to chronic diseases later in life. Research has suggested that mitochondrial function and oxidative stress may play a role in the developmental programming of chronic diseases. Having this in mind, in this review, we include evidence that mitochondrial dysfunction and oxidative stress are mechanisms by which GDM, MO, and IUGR program the offspring to chronic diseases. In this specific context, we explore the promising advantages of maternal antioxidant supplementation using compounds such as resveratrol, curcumin, N-acetylcysteine (NAC), and Mitoquinone (MitoQ) in addressing the metabolic dysfunction and oxidative stress associated with GDM, MO, and IUGR in fetoplacental and offspring metabolic health. This approach holds potential to mitigate developmental programming-related risk of chronic diseases, serving as a probable intervention for disease prevention.
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Affiliation(s)
- Mariana S. Diniz
- CNC-UC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; (M.S.D.); (C.C.M.); (C.T.); (L.F.G.)
- CIBB—Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-517 Coimbra, Portugal
- Doctoral Programme in Experimental Biology and Biomedicine (PDBEB), Institute for Interdisciplinary Research, University of Coimbra, 3004-504 Coimbra, Portugal
| | - Carina C. Magalhães
- CNC-UC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; (M.S.D.); (C.C.M.); (C.T.); (L.F.G.)
- CIBB—Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-517 Coimbra, Portugal
| | - Carolina Tocantins
- CNC-UC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; (M.S.D.); (C.C.M.); (C.T.); (L.F.G.)
- CIBB—Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-517 Coimbra, Portugal
- Doctoral Programme in Experimental Biology and Biomedicine (PDBEB), Institute for Interdisciplinary Research, University of Coimbra, 3004-504 Coimbra, Portugal
| | - Luís F. Grilo
- CNC-UC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; (M.S.D.); (C.C.M.); (C.T.); (L.F.G.)
- CIBB—Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-517 Coimbra, Portugal
- Doctoral Programme in Experimental Biology and Biomedicine (PDBEB), Institute for Interdisciplinary Research, University of Coimbra, 3004-504 Coimbra, Portugal
| | - José Teixeira
- CNC-UC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; (M.S.D.); (C.C.M.); (C.T.); (L.F.G.)
- CIBB—Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-517 Coimbra, Portugal
| | - Susana P. Pereira
- CNC-UC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; (M.S.D.); (C.C.M.); (C.T.); (L.F.G.)
- CIBB—Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-517 Coimbra, Portugal
- Laboratory of Metabolism and Exercise (LaMetEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sports, University of Porto, 4200-450 Porto, Portugal
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16
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Pinto GDA, Murgia A, Lai C, Ferreira CS, Goes VA, Guimarães DDAB, Ranquine LG, Reis DL, Struchiner CJ, Griffin JL, Burton GJ, Torres AG, El-Bacha T. Sphingolipids and acylcarnitines are altered in placentas from women with gestational diabetes mellitus. Br J Nutr 2023; 130:921-932. [PMID: 36539977 DOI: 10.1017/s000711452200397x] [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] [Indexed: 12/24/2022]
Abstract
Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy and a severe threat to pregnant people and offspring health. The molecular origins of GDM, and in particular the placental responses, are not fully known. The present study aimed to perform a comprehensive characterisation of the lipid species in placentas from pregnancies complicated with GDM using high-resolution MS lipidomics, with a particular focus on sphingolipids and acylcarnitines in a semi-targeted approach. The results indicated that despite no major disruption in lipid metabolism, placentas from GDM pregnancies showed significant alterations in sphingolipids, mostly lower abundance of total ceramides. Additionally, very long-chain ceramides and sphingomyelins with twenty-four carbons were lower, and glucosylceramides with sixteen carbons were higher in placentas from GDM pregnancies. Semi-targeted lipidomics revealed the strong impact of GDM on the placental acylcarnitine profile, particularly lower contents of medium and long-chain fatty-acyl carnitine species. The lower contents of sphingolipids may affect the secretory function of the placenta, and lower contents of long-chain fatty acylcarnitines is suggestive of mitochondrial dysfunction. These alterations in placental lipid metabolism may have consequences for fetal growth and development.
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Affiliation(s)
- Gabriela D A Pinto
- LeBioME-Bioactives, Mitochondrial and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil
| | | | - Carla Lai
- University of Cagliari, Department of Life and Environmental Science, Cagliari Via Ospedale, Cagliari, Italy
| | - Carolina S Ferreira
- LeBioME-Bioactives, Mitochondrial and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil
| | - Vanessa A Goes
- LeBioME-Bioactives, Mitochondrial and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil
| | - Deborah de A B Guimarães
- LeBioME-Bioactives, Mitochondrial and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil
| | - Layla G Ranquine
- LeBioME-Bioactives, Mitochondrial and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil
| | - Desirée L Reis
- LeBioME-Bioactives, Mitochondrial and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil
| | - Claudio J Struchiner
- School of Applied Mathematics, Fundação Getúlio Vargas, Rio de Janeiro, Brazil
- Institute of Social Medicine, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Julian L Griffin
- Department of Biochemistry, Cambridge, UK
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Graham J Burton
- Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
| | - Alexandre G Torres
- LeBioME-Bioactives, Mitochondrial and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil
- Lipid Biochemistry and Lipidomics Laboratory, Department of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Tatiana El-Bacha
- LeBioME-Bioactives, Mitochondrial and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil
- Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
- Lipid Biochemistry and Lipidomics Laboratory, Department of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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17
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Easton ZJW, Sarr O, Zhao L, Buzatto AZ, Luo X, Zhao S, Li L, Regnault TRH. An Integrated Multi-OMICS Approach Highlights Elevated Non-Esterified Fatty Acids Impact BeWo Trophoblast Metabolism and Lipid Processing. Metabolites 2023; 13:883. [PMID: 37623828 PMCID: PMC10456680 DOI: 10.3390/metabo13080883] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 07/18/2023] [Accepted: 07/19/2023] [Indexed: 08/26/2023] Open
Abstract
Maternal obesity and gestational diabetes mellitus (GDM) are linked with impaired placental function and early onset of non-communicable cardiometabolic diseases in offspring. Previous studies have highlighted that the dietary non-esterified fatty acids (NEFAs) palmitate (PA) and oleate (OA), key dietary metabolites associated with maternal obesity and GDM, are potential modulators of placental lipid processing. Using the BeWo cell line model, the current study integrated transcriptomic (mRNA microarray), metabolomic, and lipidomic readouts to characterize the underlying impacts of exogenous PA and OA on placental villous trophoblast cell metabolism. Targeted gas chromatography and thin-layer chromatography highlighted that saturated and monounsaturated NEFAs differentially impact BeWo cell lipid profiles. Furthermore, cellular lipid profiles differed when exposed to single and multiple NEFA species. Additional multi-omic analyses suggested that PA exposure is associated with enrichment in β-oxidation pathways, while OA exposure is associated with enrichment in anti-inflammatory and antioxidant pathways. Overall, this study further demonstrated that dietary PA and OA are important regulators of placental lipid metabolism. Encouraging appropriate dietary advice and implementing dietary interventions to maintain appropriate placental function by limiting excessive exposure to saturated NEFAs remain crucial in managing at-risk obese and GDM pregnancies.
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Affiliation(s)
- Zachary J. W. Easton
- Department of Physiology and Pharmacology, Western University, Medical Sciences Building Room 216, London, ON N6A 5C1, Canada; (Z.J.W.E.); (O.S.); (L.Z.)
| | - Ousseynou Sarr
- Department of Physiology and Pharmacology, Western University, Medical Sciences Building Room 216, London, ON N6A 5C1, Canada; (Z.J.W.E.); (O.S.); (L.Z.)
| | - Lin Zhao
- Department of Physiology and Pharmacology, Western University, Medical Sciences Building Room 216, London, ON N6A 5C1, Canada; (Z.J.W.E.); (O.S.); (L.Z.)
| | - Adriana Zardini Buzatto
- The Metabolomics Innovation Centre (TMIC), University of Alberta, Edmonton, AB T6G 2G2, Canada; (A.Z.B.); (X.L.); (S.Z.); (L.L.)
| | - Xian Luo
- The Metabolomics Innovation Centre (TMIC), University of Alberta, Edmonton, AB T6G 2G2, Canada; (A.Z.B.); (X.L.); (S.Z.); (L.L.)
| | - Shuang Zhao
- The Metabolomics Innovation Centre (TMIC), University of Alberta, Edmonton, AB T6G 2G2, Canada; (A.Z.B.); (X.L.); (S.Z.); (L.L.)
| | - Liang Li
- The Metabolomics Innovation Centre (TMIC), University of Alberta, Edmonton, AB T6G 2G2, Canada; (A.Z.B.); (X.L.); (S.Z.); (L.L.)
- Department of Chemistry, University of Alberta, Edmonton, AB T6G 2G2, Canada
| | - Timothy R. H. Regnault
- Department of Physiology and Pharmacology, Western University, Medical Sciences Building Room 216, London, ON N6A 5C1, Canada; (Z.J.W.E.); (O.S.); (L.Z.)
- Department of Obstetrics and Gynaecology, Western University, B2-401 London Health Science Centre-Victoria Hospital, 800 Commissioners Rd E, London, ON N6H 5W9, Canada
- Children’s Health Research Institute, 800 Commissioners Rd E, London, ON N6C 2V5, Canada
- Lawson Health Research Institute, 750 Base Line Rd E, London, ON N6C 2R5, Canada
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18
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Li L, Li L, Shao Y, Du R, Li L, Shi X, Bai Y. Calcium/calmodulin dependent protein kinase IV in trophoblast cells under insulin resistance: functional and metabolomic analyses. Mol Med 2023; 29:82. [PMID: 37386367 DOI: 10.1186/s10020-023-00669-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Accepted: 05/24/2023] [Indexed: 07/01/2023] Open
Abstract
BACKGROUND Insulin resistance (IR) is an important determinant of glucose metabolic disturbance and placental dysplasia in gestational diabetes mellitus (GDM). Calcium/calmodulin dependent protein kinase IV (CAMK4) improves insulin IR induced by a high-fat diet (HFD). The current study sought to elucidate the role and potential mechanism of CAMK4 in GDM. METHODS A GDM model was established in female C57BL/6J mice via HFD feeding for one week before mating and throughout gestation. The IR was elicited by 10-6 M insulin treatment for 48 h in HTR-8/SVneo cells and mouse primary trophoblast cells. The function of CAMK4 was investigated by transfection of overexpression plasmid in HTR-8/SVneo cells and infection of lentivirus loaded with CAMK4 encoding sequence in primary trophoblast cells. Real-time PCR, western blot, cell counting kit-8, transwell, wound healing, dual-luciferase reporter assay, and liquid chromatography/mass spectrometry-based untargeted metabolomics were performed to confirm the effects of CAMK4 on trophoblast cells. RESULTS Decreased CAMK4 expression was found in the placenta of GDM mice. CAMK4 overexpression ameliorated IR-induced viability impairment, migratory and invasive capacity inhibition, autophagy blocking, insulin signaling inactivation and glucose uptake disorder in trophoblast cells. CAMK4 also transcriptionally activated orphan nuclear receptor NUR77, and the effects of CAMK4 were abrogated by silencing of NUR77. Metabolomics analysis revealed that CAMK4 overexpression caused alterations of amino acid, lipid and carbohydrate metabolism, which were important in GDM. CONCLUSION Our results indicated that CAMK4/NUR77 axis may provide novel potential targets in GDM treatment.
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Affiliation(s)
- Ling Li
- Department of Endocrinology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, Liaoning, People's Republic of China
| | - Li Li
- Department of Endocrinology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, Liaoning, People's Republic of China
| | - Ying Shao
- Department of Endocrinology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, Liaoning, People's Republic of China
| | - Runyu Du
- Department of Endocrinology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, Liaoning, People's Republic of China
| | - Ling Li
- Department of Endocrinology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, Liaoning, People's Republic of China
| | - Xiaoguang Shi
- Department of Endocrinology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, Liaoning, People's Republic of China.
| | - Yu Bai
- Department of Endocrinology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, Liaoning, People's Republic of China.
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19
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Zhang Y, Chen L, Zhang L, Wu Y, Li L. Fasting plasma glucose and fetal ultrasound predict the occurrence of neonatal macrosomia in gestational diabetes mellitus. BMC Pregnancy Childbirth 2023; 23:269. [PMID: 37076807 PMCID: PMC10114470 DOI: 10.1186/s12884-023-05594-6] [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: 01/31/2023] [Accepted: 04/10/2023] [Indexed: 04/21/2023] Open
Abstract
OBJECTIVE The cause of fetal overgrowth during pregnancy is still unclear. This study aimed to analyze and predict the risk of macrosomia in pregnant women with gestational diabetes mellitus (GDM). METHODS This study was a retrospective study collected from October 2020 to October 2021. A total of 6072 pregnant women with a routine 75-g oral glucose tolerance test (OGTT) during 24-28 gestational weeks were screened. Nearly equal numbers of pregnant women with gestational diabetes and with normal glucose tolerance (NGT) were included in the study. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve were performed to determine the index and inflection point for predicting macrosomia occurrence. RESULTS The data of perinatal outcomes of 322 GDM and 353 NGT who had given birth to single live babies at term were analyzed. We found that significant cut-off values for the prediction of macrosomia are 5.13mmol/L in fasting plasma glucose (FPG), 12.25kg in gestational weight gain (GWG), 3,605g in ultrasound fetal weight gain (FWG) and 124mm in amniotic fluid index (AFI).The area under the ROC curve of this predictive model combined all variables reached 0.953 (95% CI: 0.914 ~ 0.993) with a sensitivity of 95.0% and a specificity of 85.4%. CONCLUSIONS FPG is positively associated with newborn birth weight. An early intervention to prevent macrosomia may be possible by combining maternal GWG, FPG, FWG, and AFI in gestational diabetes.
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Affiliation(s)
- Yuting Zhang
- The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
- Shantou University Medical College, Shantou, Guangdong, China
| | - Linying Chen
- The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
- Shantou University Medical College, Shantou, Guangdong, China
| | - Lijing Zhang
- The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Yudan Wu
- The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Li Li
- The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
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20
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Ferreira CS, Pinto GDA, Reis DL, Vigor C, Goes VA, Guimarães DDAB, Mucci DB, Belcastro L, Saraiva MA, Oger C, Galano JM, Sardinha FLC, Torres AG, Durand T, Burton GJ, El-Bacha T. Placental F 4-Neuroprostanes and F 2-Isoprostanes are altered in gestational diabetes mellitus and maternal obesity. Prostaglandins Leukot Essent Fatty Acids 2023; 189:102529. [PMID: 36608621 DOI: 10.1016/j.plefa.2022.102529] [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: 08/28/2022] [Revised: 11/30/2022] [Accepted: 12/23/2022] [Indexed: 12/26/2022]
Abstract
We investigated whether gestational diabetes mellitus (GDM) associated with maternal obesity modifies the placental profile of F4-Neuroprostanes and F2-Isoprostanes, metabolites of non-enzymatic oxidation of docosahexaenoic acid (DHA) and arachidonic acid (AA), respectively. Twenty-five placental samples were divided into lean (n=11), obesity (n=7) and overweight/obesity+GDM (n=7) groups. F4-Neuroprostanes and F2-Isoprostanes were higher in obesity compared to lean controls, but reduced to levels similar to lean women when obesity is further complicated with GDM. Lower content of F2-Isoprostanes suggests adaptive placental responses in GDM attenuating oxidative stress. However, low levels of placental F4-Neuroprostanes may indicate impaired DHA metabolism in GDM, affecting fetal development and offspring health. These results were not related to differences in placental content of DHA, AA and polyunsaturated fatty acids status nor to maternal diet or gestational weight gain. Placental DHA and AA metabolism differs in obesity and GDM, highlighting the importance of investigating the signalling roles of F4-Neuroprostanes and F2-Isoprostanes in the human term placenta.
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Affiliation(s)
- Carolina S Ferreira
- LeBioME-Bioactives, Mitochondria and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil
| | - Gabriela D A Pinto
- LeBioME-Bioactives, Mitochondria and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil
| | - Desirée L Reis
- LeBioME-Bioactives, Mitochondria and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil
| | - Claire Vigor
- Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, Université de Montpellier, CNRS, ENSCM, Bâtiment Balard, 1919 route de Mende, CEDEX 5, 34293 Montpellier, France
| | - Vanessa A Goes
- LeBioME-Bioactives, Mitochondria and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil
| | - Deborah de A B Guimarães
- LeBioME-Bioactives, Mitochondria and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil
| | - Daniela B Mucci
- Laboratory of Nutritional Biochemistry, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil
| | - Livia Belcastro
- Laboratory of Nutritional Biochemistry, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil
| | - Marcelle A Saraiva
- Laboratory of Nutritional Biochemistry, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil
| | - Camille Oger
- Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, Université de Montpellier, CNRS, ENSCM, Bâtiment Balard, 1919 route de Mende, CEDEX 5, 34293 Montpellier, France
| | - Jean-Marie Galano
- Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, Université de Montpellier, CNRS, ENSCM, Bâtiment Balard, 1919 route de Mende, CEDEX 5, 34293 Montpellier, France
| | - Fátima L C Sardinha
- Laboratory of Nutritional Biochemistry, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil
| | - Alexandre G Torres
- LeBioME-Bioactives, Mitochondria and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil; Laboratory of Biochemistry and Chemistry of Lipids, Department of Chemistry, Universidade Federal do Rio de Janeiro, 21941-909 Rio de Janeiro, Brazil
| | - Thierry Durand
- Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, Université de Montpellier, CNRS, ENSCM, Bâtiment Balard, 1919 route de Mende, CEDEX 5, 34293 Montpellier, France
| | - Graham J Burton
- Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB23EG, United Kingdom
| | - Tatiana El-Bacha
- LeBioME-Bioactives, Mitochondria and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil; Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB23EG, United Kingdom.
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21
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Gestational Diabetes Mellitus and Small-for-Gestational-Age: An Insight into the Placental Molecular Biomarkers. Int J Mol Sci 2023; 24:ijms24032240. [PMID: 36768564 PMCID: PMC9916826 DOI: 10.3390/ijms24032240] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/13/2023] [Accepted: 01/17/2023] [Indexed: 01/24/2023] Open
Abstract
Gestational diabetes mellitus (GDM) and small-for-gestational-age (SGA) are two metabolic-related diseases that could affect women during pregnancy. Considering that the chorionic villi (CVs) are crucial structures for the feto-maternal exchange, the alterations in their conformation have been linked to an imbalanced metabolic environment of placenta. In this study, a multidisciplinary approach has been carried out to describe the changes occurring in the placental CVs of GDM and SGA patients. The results revealed higher levels of superoxide dismutase 1 (SOD-1) and catalase (CAT), especially in the GDM placentae, which could be correlated with the hyperglycemic environment characteristic of this pathology. Furthermore, spectroscopy and histologic analyses revealed that both pathologies modify the placental lipid composition altering its structure. However, SGA induces lipid peroxidation and reduces collagen deposition within the CVs. Since the endocannabinoid system (ECS) is involved in placentation and different metabolic activities, the cannabinoid receptor 1 (CB1) and transient receptor potential cation channel subfamily V member 1 (TRPV-1) were analyzed. No changes have been observed either at general or specific levels in the CVs comparing control and pathological samples, suggesting the non-involvement of the cannabinoid system in these two pathologies.
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22
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A comprehensive investigation of human endogenous retroviral syncytin proteins and their receptors in men with normozoospermia and impaired semen quality. J Assist Reprod Genet 2023; 40:97-111. [PMID: 36469256 PMCID: PMC9734899 DOI: 10.1007/s10815-022-02673-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 11/25/2022] [Indexed: 12/07/2022] Open
Abstract
PURPOSE The study aims to investigate first the presence of Syncytin 2 and its receptor, MFSD2, in human sperm, and second whether the expressions of Syncytin 1, Syncytin 2, and their receptors, SLC1A5 and MFSD2, differ between normozoospermic, asthenozoospermic, oligozoospermic, and oligoasthenozoospermic human sperm samples. METHODS The localization patterns and expression levels of syncytins and their receptors were evaluated in normozoospermic (concentration = 88.9 ± 5.5 × 106, motility = 79.2 ± 3.15%, n = 30), asthenozoospermic (concentration = 51.7 ± 7.18 × 106, motility = 24.0 ± 3.12%, n = 15), mild oligozoospermic (concentration = 13.5 ± 2.17 × 106, motility = 72.1 ± 6.5%, n = 15), moderate oligozoospermic (concentration = 8.4 ± 3.21 × 106, motility = 65.1 ± 8.9%, n = 15), severe oligozoospermic (concentration = 2.1 ± 1.01 × 106, motility = 67.5 ± 3.2%, n = 15), and oligoasthenozoospermic (concentration = 5.5 ± 3.21 × 106, motility = 18.5 ± 1.2%, n = 15) samples by immunofluorescence staining and western blot. RESULTS Syncytins and their receptors visualized by immunofluorescence showed similar staining patterns with slight staining of the tail in all spermatozoa regardless of normozoospermia, asthenozoospermia, oligozoospermia, or oligoasthenozoospermia. The localization patterns were categorized as equatorial segment, midpiece region, acrosome, and post-acrosomal areas. The combined staining patterns were also detected as acrosomal cap plus post acrosomal region, the midpiece plus equatorial segment, and midpiece plus acrosomal region. However, some sperm cells were categorized as non-stained. Both syncytin proteins were most intensely localized in the midpiece region, while their receptors were predominantly present in the midpiece plus acrosomal region. Conspicuously, syncytins and their receptors showed decreased expression in asthenozospermic, oligozoospermic, and oligoasthenozoospermic samples compared to normozoospermic samples. CONCLUSION The expression patterns of HERV-derived syncytins and their receptors were identical regardless of the spermatozoa in men with normozoospermia versus impaired semen quality. Further, asthenozoospermia, oligozoospermia, and oligoasthenozoospermia as male fertility issues are associated with decreased expression of both syncytins and their receptors.
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23
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Du M, Chen Y, Dong M, Liang Z, Chen D. Down-Regulation of PLAC1 in the Placenta of Gestational Diabetes Mellitus Patients and its Clinical Significance. CLIN EXP OBSTET GYN 2022; 49. [DOI: 10.31083/j.ceog4910233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/01/2024]
Abstract
Background: Placenta-specific 1 (PLAC1) is specifically expressed in the placenta and plays a fundamental role in placenta function. Aberrant expression of PLAC1 has been reported in pregnancy-related disorders; however, its expression in gestational diabetes mellitus (GDM) has not been clearly elucidated. This study aimed to investigate the expression of PLAC1 in the placenta of GDM patients, and its relationship with clinical characteristics. Methods: This was a case-control study. Placental tissues were collected from 37 GDM patients (GDM group) and 38 pregnant women with normal glucose tolerance (control group), matched with respect to maternal age and gestational weeks. We examined the expression of PLAC1 in the placenta of both groups and determined its association with clinical indicators. The localization of PLAC1 was confirmed by immunohistochemistry analyses. Results: PLAC1 expression was significantly lower in the placenta of GDM patients. For the control group, PLAC1 was positively correlated with pre-pregnancy body mass index (BMI), BMI at delivery, the fasting insulin, triglyceride levels, and homeostasis model assessment during delivery. In the case of GDM patients, there was no correlation between PLAC1 and these indices. Additionally, PLAC1 protein was mainly expressed in the cytoplasm of syncytiotrophoblasts and chorionic stromal cells. Conclusions: The expression of PLAC1 was reduced in the GDM placenta, which provides insight into the pathophysiological changes occurring in the placenta of these patients.
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Affiliation(s)
- Mengkai Du
- Departments of Obstetrics, Women's Hospital, School of Medicine, Zhejiang University, 310058 Hangzhou, Zhejiang, China
| | - Yanmin Chen
- Departments of Obstetrics, Women's Hospital, School of Medicine, Zhejiang University, 310058 Hangzhou, Zhejiang, China
| | - Minyue Dong
- Department of Reproductive Genetics, Women's Hospital, School of Medicine, Zhejiang University, 310058 Hangzhou, Zhejiang, China
| | - Zhaoxia Liang
- Departments of Obstetrics, Women's Hospital, School of Medicine, Zhejiang University, 310058 Hangzhou, Zhejiang, China
| | - Danqing Chen
- Departments of Obstetrics, Women's Hospital, School of Medicine, Zhejiang University, 310058 Hangzhou, Zhejiang, China
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24
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Wang S, Ning J, Huai J, Yang H. Hyperglycemia in Pregnancy-Associated Oxidative Stress Augments Altered Placental Glucose Transporter 1 Trafficking via AMPKα/p38MAPK Signaling Cascade. Int J Mol Sci 2022; 23:ijms23158572. [PMID: 35955706 PMCID: PMC9369398 DOI: 10.3390/ijms23158572] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Revised: 07/29/2022] [Accepted: 07/29/2022] [Indexed: 11/16/2022] Open
Abstract
GLUT1, being a ubiquitous transporter isoform, is considered primarily responsible for glucose uptake during glycolysis. However, there is still uncertainty about the regulatory mechanisms of GLUT1 in hyperglycemia in pregnancy (HIP, PGDM, and GDM) accompanied by abnormal oxidative stress responses. In the present study, it was observed that the glycolysis was enhanced in GDM and PGDM pregnancies. In line with this, the antioxidant system was disturbed and GLUT1 expression was increased due to diabetes impairment in both placental tissues and in vitro BeWo cells. GLUT1 responded to high glucose stimulation through p38MAPK in an AMPKα-dependent manner. Both the medical-mediated and genetic depletion of p38MAPK in BeWo cells could suppress GLUT1 expression and OS-induced proapoptotic effects. Furthermore, blocking AMPKα with an inhibitor or siRNA strategy promoted p38MAPK, GLUT1, and proapoptotic molecules expression and vice versa. In general, a new GLUT1 regulation pathway was identified, which could exert effects on placental transport function through the AMPKα-p38MAPK pathway. AMPKα may be a therapeutic target in HIP for alleviating diabetes insults.
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Affiliation(s)
- Shuxian Wang
- Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing 100034, China; (S.W.); (J.N.); (J.H.)
- Beijing Key Laboratory of Maternal Fetal Medicine of Gestational Diabetes Mellitus, Beijing 100034, China
| | - Jie Ning
- Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing 100034, China; (S.W.); (J.N.); (J.H.)
- Beijing Key Laboratory of Maternal Fetal Medicine of Gestational Diabetes Mellitus, Beijing 100034, China
| | - Jing Huai
- Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing 100034, China; (S.W.); (J.N.); (J.H.)
- Beijing Key Laboratory of Maternal Fetal Medicine of Gestational Diabetes Mellitus, Beijing 100034, China
| | - Huixia Yang
- Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing 100034, China; (S.W.); (J.N.); (J.H.)
- Beijing Key Laboratory of Maternal Fetal Medicine of Gestational Diabetes Mellitus, Beijing 100034, China
- Correspondence:
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25
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Wu B, Chen Y, Clarke R, Akala E, Yang P, He B, Gao H. AMPK Signaling Regulates Mitophagy and Mitochondrial ATP Production in Human Trophoblast Cell Line BeWo. FRONT BIOSCI-LANDMRK 2022; 27:118. [PMID: 35468677 PMCID: PMC9830999 DOI: 10.31083/j.fbl2704118] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 03/03/2022] [Accepted: 03/08/2022] [Indexed: 01/18/2023]
Abstract
INTRODUCTION Accumulating evidence suggests that mitochondrial structural and functional defects are present in human placentas affected by pregnancy related disorders, but mitophagy pathways in human trophoblast cells/placental tissues have not been investigated. METHODS In this study, we investigated three major mitophagy pathways mediated by PRKN, FUNDC1, and BNIP3/BNIP3L in response to AMPK activation by AICAR and knockdown of PRKAA1/2 (AKD) in human trophoblast cell line BeWo and the effect of AKD on mitochondrial membrane potential and ATP production. RESULTS Autophagy flux assay demonstrated that AMPK signaling activation stimulates autophagy, evidenced increased LC3II and SQSTM1 protein abundance in the whole cell lysates and mitochondrial fractions, and mitophagy flux assay demonstrated that the activation of AMPK signaling stimulates mitophagy via PRKN and FUNDC1 mediated but not BNIP3/BNIP3L mediated pathways. The stimulatory regulation of AMPK signaling on mitophagy was confirmed by AKD which reduced the abundance of LC3II, SQSTM1, PRKN, and FUNDC1 proteins, but increased the abundance of BNIP3/BNIP3L proteins. Coincidently, AKD resulted in elevated mitochondrial membrane potential and reduced mitochondrial ATP production, compared to control BeWo cells. CONCLUSIONS In summary, AMPK signaling stimulates mitophagy in human trophoblast cells via PRKN and FUNDC1 mediated mitophagy pathways and AMPK regulated mitophagy contributes to the maintenance of mitochondrial membrane potential and mitochondrial ATP production.
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Affiliation(s)
- Bin Wu
- Department of Reproductive Medicine, Central Hospital Affiliated to Shandong First Medical University, 250013 Jinan, Shandong, China
| | - Yun Chen
- Rocket Pharmaceuticals, Inc., Cranbury, NJ 08512, USA
| | - Robert Clarke
- The Hormel Institute, University of Minnesota, Austin, MN 55912, USA
| | - Emmanuel Akala
- Department of Pharmaceutical Sciences, College of Pharmacy, Howard University, Washington, DC 20060, USA
| | - Peixin Yang
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Bin He
- Reproductive Physiology Laboratory, National Research Institute for Family Planning, 100081 Beijing, China
| | - Haijun Gao
- Department of Physiology and Biophysics, College of Medicine, Howard University, Washington, DC 20059, USA,Correspondence: (Haijun Gao)
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Rees A, Richards O, Chambers M, Jenkins BJ, Cronin JG, Thornton CA. Immunometabolic adaptation and immune plasticity in pregnancy and the bi-directional effects of obesity. Clin Exp Immunol 2022; 208:132-146. [PMID: 35348641 PMCID: PMC9188350 DOI: 10.1093/cei/uxac003] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 01/24/2022] [Indexed: 01/25/2023] Open
Abstract
Mandatory maternal metabolic and immunological changes are essential to pregnancy success. Parallel changes in metabolism and immune function make immunometabolism an attractive mechanism to enable dynamic immune adaptation during pregnancy. Immunometabolism is a burgeoning field with the underlying principle being that cellular metabolism underpins immune cell function. With whole body changes to the metabolism of carbohydrates, protein and lipids well recognised to occur in pregnancy and our growing understanding of immunometabolism as a determinant of immunoinflammatory effector responses, it would seem reasonable to expect immune plasticity during pregnancy to be linked to changes in the availability and handling of multiple nutrient energy sources by immune cells. While studies of immunometabolism in pregnancy are only just beginning, the recognised bi-directional interaction between metabolism and immune function in the metabolic disorder obesity might provide some of the earliest insights into the role of immunometabolism in immune plasticity in pregnancy. Characterised by chronic low-grade inflammation including in pregnant women, obesity is associated with numerous adverse outcomes during pregnancy and beyond for both mother and child. Concurrent changes in metabolism and immunoinflammation are consistently described but any causative link is not well established. Here we provide an overview of the metabolic and immunological changes that occur in pregnancy and how these might contribute to healthy versus adverse pregnancy outcomes with special consideration of possible interactions with obesity.
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Affiliation(s)
- April Rees
- Institute of Life Science, Swansea University Medical School, Swansea, Wales SA2 8PP, UK
| | - Oliver Richards
- Institute of Life Science, Swansea University Medical School, Swansea, Wales SA2 8PP, UK
| | - Megan Chambers
- Institute of Life Science, Swansea University Medical School, Swansea, Wales SA2 8PP, UK
| | - Benjamin J Jenkins
- Institute of Life Science, Swansea University Medical School, Swansea, Wales SA2 8PP, UK
| | - James G Cronin
- Institute of Life Science, Swansea University Medical School, Swansea, Wales SA2 8PP, UK
| | - Catherine A Thornton
- Corresponding author: Cathy Thornton, ILS1, Swansea University Medical School, Singleton Campus, Swansea University, Swansea, Wales SA2 8PP, UK.
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27
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Stern C, Schwarz S, Moser G, Cvitic S, Jantscher-Krenn E, Gauster M, Hiden U. Placental Endocrine Activity: Adaptation and Disruption of Maternal Glucose Metabolism in Pregnancy and the Influence of Fetal Sex. Int J Mol Sci 2021; 22:12722. [PMID: 34884524 PMCID: PMC8657775 DOI: 10.3390/ijms222312722] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 11/16/2021] [Accepted: 11/17/2021] [Indexed: 02/07/2023] Open
Abstract
The placenta is an endocrine fetal organ, which secretes a plethora of steroid- and proteo-hormones, metabolic proteins, growth factors, and cytokines in order to adapt maternal physiology to pregnancy. Central to the growth of the fetus is the supply with nutrients, foremost with glucose. Therefore, during pregnancy, maternal insulin resistance arises, which elevates maternal blood glucose levels, and consequently ensures an adequate glucose supply for the developing fetus. At the same time, maternal β-cell mass and function increase to compensate for the higher insulin demand. These adaptations are also regulated by the endocrine function of the placenta. Excessive insulin resistance or the inability to increase insulin production accordingly disrupts physiological modulation of pregnancy mediated glucose metabolism and may cause maternal gestational diabetes (GDM). A growing body of evidence suggests that this adaptation of maternal glucose metabolism differs between pregnancies carrying a girl vs. pregnancies carrying a boy. Moreover, the risk of developing GDM differs depending on the sex of the fetus. Sex differences in placenta derived hormones and bioactive proteins, which adapt and modulate maternal glucose metabolism, are likely to contribute to this sexual dimorphism. This review provides an overview on the adaptation and maladaptation of maternal glucose metabolism by placenta-derived factors, and highlights sex differences in this regulatory network.
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Affiliation(s)
- Christina Stern
- Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria
| | - Sarah Schwarz
- Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria
| | - Gerit Moser
- Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, Austria
| | - Silvija Cvitic
- Research Unit of Analytical Mass Spectrometry, Cell Biology and Biochemistry of Inborn Errors of Metabolism, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, 8036 Graz, Austria
| | | | - Martin Gauster
- Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, Austria
| | - Ursula Hiden
- Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria
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Shen D, Lu Y, Li G, Hu M, Li S, Ju H, Zhang M, Wang X. Mechanism of neutrophil extracellular traps generation and their role in trophoblasts apoptosis in gestational diabetes mellitus. Cell Signal 2021; 88:110168. [PMID: 34634453 DOI: 10.1016/j.cellsig.2021.110168] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 09/24/2021] [Accepted: 10/05/2021] [Indexed: 12/23/2022]
Abstract
Gestational diabetes mellitus (GDM) is a metabolic syndrome occurring in pregnant women and increases the risk of placental dysplasia. Neutrophil extracellular traps (NETs) may play a critical role in placental dysplasia. NETosis (neutrophil cell death by NET release) depends on NADPH/ROS pathway. In view of the adiponectin which is widely believed to be reduced in GDM patients suppresses NADPH oxidase and ROS generation of neutrophil. We speculate that increased NET release is associated with hypoadiponectinemia. Trophoblast apoptosis is significantly increased in GDM patients, but it is not clear whether NETs promotes cell apoptosis. This study aims to reveal the mechanism of Neutrophil Extracellular Traps generation and their role in trophoblast apoptosis in Gestational Diabetes Mellitus. We investigated the generation of NETs by cell-free DNA (cf-DNA) quantification, live-cell imaging, and reactive oxygen species (ROS) measurement. ERK1/2 and p38 MAPK signalling pathway proteins were detected by western blotting. The Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and western blotting were performed to explore the effects of NETs on trophoblast apoptosis. We found that adiponectin inhibited NET release by suppressing ROS production, and p38 MAPK and ERK1/2 proteins were involved in the process. Further, NETs promoted trophoblast apoptosis by activating the ROS-dependent mitochondrial pathway, which is mediated by ERK1/2 signalling. The current study demonstrated that hypoadiponectinemia is the cause of NETs formation and NETs promoting trophoblast apoptosis.
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Affiliation(s)
- Di Shen
- Department of Obstetrics and Gynaecology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, 324 Jingwu Street, Jinan, Shandong 250021, China; Department of Obstetrics and Gynaecology, Maternal and Child Health Care Hospital of Shandong Provincial, Cheeloo College of Medicine, Shandong University, 238 Jingshi East Road, Jinan, Shandong 250014, China
| | - Yuan Lu
- Department of Obstetrics and Gynaecology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, 324 Jingwu Street, Jinan, Shandong 250021, China
| | - Guangzhen Li
- Department of General Surgery, Qilu Hospital of Shandong University, 107 Wenhua West Road, 251000, Jinan, China
| | - Min Hu
- Department of Obstetrics and Gynaecology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, 324 Jingwu Street, Jinan, Shandong 250021, China
| | - Shanling Li
- Department of Obstetrics and Gynaecology, Maternal and Child Health Care Hospital of Shandong Provincial, Cheeloo College of Medicine, Shandong University, 238 Jingshi East Road, Jinan, Shandong 250014, China
| | - Hui Ju
- Department of Obstetrics and Gynaecology, Maternal and Child Health Care Hospital of Shandong Provincial, Cheeloo College of Medicine, Shandong University, 238 Jingshi East Road, Jinan, Shandong 250014, China
| | - Meihua Zhang
- The Laboratory of Placenta-Related Diseases, Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, 238 Jingshi East Road, Jinan, Shandong 250014, China
| | - Xietong Wang
- Department of Obstetrics and Gynaecology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, 324 Jingwu Street, Jinan, Shandong 250021, China; Department of Obstetrics and Gynaecology, Maternal and Child Health Care Hospital of Shandong Provincial, Cheeloo College of Medicine, Shandong University, 238 Jingshi East Road, Jinan, Shandong 250014, China; The Laboratory of Placenta-Related Diseases, Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, 238 Jingshi East Road, Jinan, Shandong 250014, China.
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29
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Olmos-Ortiz A, Flores-Espinosa P, Díaz L, Velázquez P, Ramírez-Isarraraz C, Zaga-Clavellina V. Immunoendocrine Dysregulation during Gestational Diabetes Mellitus: The Central Role of the Placenta. Int J Mol Sci 2021; 22:8087. [PMID: 34360849 PMCID: PMC8348825 DOI: 10.3390/ijms22158087] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 07/15/2021] [Accepted: 07/26/2021] [Indexed: 02/07/2023] Open
Abstract
Gestational Diabetes Mellitus (GDM) is a transitory metabolic condition caused by dysregulation triggered by intolerance to carbohydrates, dysfunction of beta-pancreatic and endothelial cells, and insulin resistance during pregnancy. However, this disease includes not only changes related to metabolic distress but also placental immunoendocrine adaptations, resulting in harmful effects to the mother and fetus. In this review, we focus on the placenta as an immuno-endocrine organ that can recognize and respond to the hyperglycemic environment. It synthesizes diverse chemicals that play a role in inflammation, innate defense, endocrine response, oxidative stress, and angiogenesis, all associated with different perinatal outcomes.
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Affiliation(s)
- Andrea Olmos-Ortiz
- Departamento de Inmunobioquímica, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes (INPer), Ciudad de México 11000, Mexico; (A.O.-O.); (P.F.-E.)
| | - Pilar Flores-Espinosa
- Departamento de Inmunobioquímica, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes (INPer), Ciudad de México 11000, Mexico; (A.O.-O.); (P.F.-E.)
| | - Lorenza Díaz
- Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México 14080, Mexico;
| | - Pilar Velázquez
- Departamento de Ginecología y Obstetricia, Hospital Ángeles México, Ciudad de México 11800, Mexico;
| | - Carlos Ramírez-Isarraraz
- Clínica de Urología Ginecológica, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes (INPer), Ciudad de México 11000, Mexico;
| | - Verónica Zaga-Clavellina
- Departamento de Fisiología y Desarrollo Celular, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes (INPer), Ciudad de México 11000, Mexico
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