Bisphenol A and its structural analogues exhibit differential potential to induce mitochondrial dysfunction and apoptosis in human granulosa cells

Food and Chemical Toxicology, Journal Year: 2024, Volume and Issue: 188, P. 114713 - 114713

Published: May 1, 2024

Language: Английский

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Molecular mechanisms of cadmium-induced cytotoxicity in human ovarian granulosa cells identified using integrated omics

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 272, P. 116026 - 116026

Published: Jan. 30, 2024

Epidemiological and clinical data have demonstrated that exposure to cadmium (Cd), a toxic heavy metal, is associated with an increased risk of female infertility. Granulosa cells, the main somatic cells comprising ovarian follicles, are one targets Cd in ovaries. However, mechanism by which induces cytotoxicity granulosa has not been fully elucidated. In this study, we exposed human (KGN cells) conducted vitro cell experiments multi-omics (metabolomics transcriptomics) methods elucidate these mechanisms. was found only induce apoptosis KGN but also further reduced mitochondrial function decreasing membrane potential, ATP production, respiratory chain complex activity as well increasing reactive oxygen species (ROS) production. A total 443 differentially expressed metabolites (160 upregulated 283 downregulated) 5200 genes (4634 566 were observed exposed-cells. The showed interfered citric acid cycle (TCA cycle), amino (including alanine, glycine, serine, threonine, arginine, proline) metabolism, calcium signaling. These findings help better potential toxicity mechanisms on ovary.

Language: Английский

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Mechanism of elevated LH/FSH ratio in lean PCOS revisited: a path analysis

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: April 8, 2024

Abstract Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting 5–20% of reproductive-age women. However, treatment PCOS mainly based on symptoms and not its pathophysiology. Neuroendocrine disturbance, as shown by an elevated LH/FSH ratio in patients, was thought to be central mechanism syndrome, especially lean PCOS. LH FSH secretion are influenced GnRH pulsatility neurons hypothalamus. Kisspeptin main regulator secretion, whereas neurokinin B (NKB) dynorphin regulate kisspeptin KNDy neurons. This study aims deepen understanding neuroendocrine patients potential pathophysiology-based therapy. A cross-sectional performed at Dr. Cipto Mangunkusumo Kencana Hospital IMERI UI HRIFP cluster with 110 subjects. LH, FSH, ratio, kisspeptin, NKB, dynorphin, leptin, adiponectin, AMH, fasting blood glucose, insulin, HOMA-IR, testosterone, SHBG were measured. Bivariate path analyses determine relationship between variables. There a negative association while NKB levels associated kisspeptin. no direct ratio; interestingly, positively both bivariate pathway analyses. AMH correlated Path analysis showed PCOS, Furthermore, there correlation but did show significant ratio. HOMA-IR negatively adiponectin leptin FAI levels. In conclusion, correlates directly showing important role neuroendocrinology From analysis, also intermediary variable Interestingly, this found positive found. Further research needed investigate therapeutic targets management patients.

Language: Английский

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Endocrine-disrupting chemicals and hormonal profiles in PCOS women: A comparative study between urban and rural environment

Reproductive Toxicology, Journal Year: 2024, Volume and Issue: 125, P. 108562 - 108562

Published: Feb. 28, 2024

Language: Английский

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Pathophysiological Effects of Contemporary Lifestyle on Evolutionary-Conserved Survival Mechanisms in Polycystic Ovary Syndrome

Life, Journal Year: 2023, Volume and Issue: 13(4), P. 1056 - 1056

Published: April 20, 2023

Polycystic ovary syndrome (PCOS) is increasingly being characterized as an evolutionary mismatch disorder that presents with a complex mixture of metabolic and endocrine symptoms. The Evolutionary Model proposes PCOS arises from collection inherited polymorphisms have been consistently demonstrated in variety ethnic groups races. In utero developmental programming susceptible genomic variants are thought to predispose the offspring develop PCOS. Postnatal exposure lifestyle environmental risk factors results epigenetic activation developmentally programmed genes disturbance hallmarks health. resulting pathophysiological changes represent consequences poor-quality diet, sedentary behaviour, disrupting chemicals, stress, circadian disruption, other factors. Emerging evidence suggests lifestyle-induced gastrointestinal dysbiosis plays central role pathogenesis Lifestyle exposures initiate result microbiome (dysbiosis), immune dysregulation (chronic inflammation), altered metabolism (insulin resistance), reproductive imbalance (hyperandrogenism), nervous system dysfunction (neuroendocrine autonomic system). can be progressive condition leads obesity, gestational diabetes, type two metabolic-associated fatty liver disease, syndrome, cardiovascular cancer. This review explores mechanisms underpin between ancient survival pathways contemporary involved pathophysiology

Language: Английский

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High dietary copper intake induces perturbations in the gut microbiota and affects host ovarian follicle development

Ecotoxicology and Environmental Safety, Journal Year: 2023, Volume and Issue: 255, P. 114810 - 114810

Published: March 20, 2023

Increasing evidence has shown that gut microbes play an important role in the reproductive endocrine system and development of polycystic ovary syndrome (PCOS). However, whether environmental factors are involved these microbiota alterations seldom been studied. In this study, we aimed to explore crucial imbalanced on abnormal ovarian follicle induced by Cu. A 1:1 matched case-control study with 181 PCOS patients controls was conducted using a propensity score matching protocol. Information regarding dietary Cu intake obtained from face-to-face interview. Alterations were detected high-throughput 16 S rDNA sequencing. The results showed positively correlated risk PCOS, threshold approximately 1.992 mg/d. Compared those intakes lower than mg/d, who had higher 1.813-fold increased (OR=1.813, 95% CI: 1.150–2.857). relative abundance Bacteroides (P = 0.003), played partial mediating between exposure (Pindirect effect=0.026, 0.002–0.072). addition, animal model through diet can induce disorder; increase serum levels LPS, MDA, IL-6; alter host steroidogenesis affect development. Staphylococcus CYP17A1 (Pg_Staphylococcus=0.083, 0.001–0.228). Overall, shows long-term high composition microbiota, cause inflammation oxidative stress, then interfere hormone signaling, ultimately affecting

Language: Английский

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The Pathophysiological Mechanism and Clinical Treatment of Polycystic Ovary Syndrome: A Molecular and Cellular Review of the Literature

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 9037 - 9037

Published: Aug. 20, 2024

Polycystic ovary syndrome (PCOS) is a prevalent metabolic disorder among women of reproductive age, characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. The pathogenesis PCOS involves complex interplay genetic environmental factors, including insulin resistance (IR) resultant hyperinsulinemia. Insulin receptors, primarily in skeletal muscle, liver, adipose tissue, activate downstream signaling pathways like PI3K-AKT MAPK-ERK upon binding. These regulate glucose uptake, storage, lipid metabolism. Genome-wide association studies (GWASs) have identified several candidate genes related to steroidogenesis signaling. Environmental factors such as endocrine-disrupting chemicals lifestyle choices also exacerbate traits. Other than modification surgical intervention, management strategies for can be achieved using pharmacological treatments antiandrogens, metformin, thiazolidinediones, aromatase inhibitor, ovulation drugs improve sensitivity function, well combined oral contraceptives with or without cyproterone resume menstrual regularity. Despite the pathophysiology significant economic burden PCOS, comprehensive understanding its molecular cellular mechanisms crucial developing effective public health policies treatment strategies. Nevertheless, many unknown aspects detailed actions, along safety effectiveness treatment, warrant further investigation.

Language: Английский

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Unraveling the complexity of the molecular pathways associated with polycystic ovary syndrome (PCOS) and identifying molecular targets for therapeutic development: a review of literature

Middle East Fertility Society Journal, Journal Year: 2023, Volume and Issue: 28(1)

Published: June 30, 2023

Abstract Background Polycystic ovary syndrome (PCOS) is the most typical endocrine disorder affecting women worldwide. Although etiology of PCOS not fully understood, genetic factors are believed to play an essential role in its pathogenesis. Hence, this paper presents a review outcome functional enrichment analysis pathways associated with phenotypes for identification potential molecular targets as area further research therapeutic development PCOS. Method It implementation comprehensive literature search database including PubMed and Google Scholar genes HSD3B2, PPARG, PPP1R3A, LMNA, AMH their roles metabolic Findings The LMNA emerged important relation PCOS, suggesting that they could key regulating different aspects These findings provide valuable insights into mechanisms underlie complex condition highlight targeting these specific promising approach developing effective treatments Conclusion was concluded exploring new contributing study recommended on improving health quality life battling

Language: Английский

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Regulation of Insulin Resistance, Lipid Profile and Glucose Metabolism Associated with Polycystic Ovary Syndrome by Tinospora cordifolia

Nutrients, Journal Year: 2023, Volume and Issue: 15(10), P. 2238 - 2238

Published: May 9, 2023

Background: The plant Tinospora cordifolia (TC), traditionally known as guduchi or giloy, is used for a number of health conditions nutritional supplement and rejuvenation medicine. Its supplementary products are recommended wide range issues, including diabetes, menstruation discomfort, fever, obesity, inflammation, more. Unfortunately, there has not been extensive research into its effectiveness in treating managing insulin resistance, lipid carbohydrate metabolism, hormonal imbalance, metabolic syndrome-associated polycystic ovary syndrome (PCOS). Methods: Consequently, the present study was designed to induce dyslipidemia, abnormality, hyperglycemia, menstrual disturbance PCOS using dehydroepiandrosterone (DHEA) mice effect oral TC extracts on these factors by ancient modern technologies. During 21-day study, 6 mg/100 g/day DHEA given female mice. Levels glucose, insulin, lipids, hormones were estimated. In addition being seen with naked eye, morphological microscopic changes also observed histology slides. Results: outcomes show that pretreatment preparations significantly improved biochemical histological abnormalities Diestrus phase only DHEA-treated animals, while cornified epithelial cells TC-treated Pretreatment satva showed significant (p < 0.001) reductions body weight compared placebo. Fasting blood 1-h OGTT, 2-h OGTT levels all lower satva- oil-treated animals comparison disease control group 0.001). Treatment resulted normalization estradiol, progesterone, testosterone 0.05). extract profiles 0.001), LH/FSH ratios 0.01), fasting HOMA-IR HOMA-Beta QUICKI Both macroscopic alterations be restored after treatment. After treated satva, oil, hydroalcoholic extract, severity decreased 54.86%. Conclusions: These findings lead us conclusion supplements useful associated symptoms. It additional conducted determine molecular mechanism action PCOS-related profiles. We recommend further clinical studies explore efficacy and/or PCOS.

Language: Английский

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Enhancing angiogenesis and inhibiting apoptosis: evaluating the therapeutic efficacy of bone marrow mesenchymal stem cell-derived exosomes in a DHEA-induced PCOS mouse model

Journal of Ovarian Research, Journal Year: 2024, Volume and Issue: 17(1)

Published: June 5, 2024

Polycystic Ovary Syndrome (PCOS) is a widespread endocrine disorder among women, characterized by symptoms like ovarian cysts, hormonal imbalance, and metabolic issues. This research evaluates the therapeutic potential of Bone Marrow Mesenchymal Stem Cell-derived exosomes (BMSC-Exo) in treating PCOS within mouse model.

Language: Английский

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