Polycystic ovary syndrome (PCOS) and oxidative stress

Journal of Integrated Science and Technology, Год журнала: 2024, Номер 12(3)

Опубликована: Янв. 3, 2024

Polycystic Ovary Syndrome (PCOS) affects about 10% of women reproductive age, characterized by hyperandrogenism, anovulation, and polycystic ovaries. Despite extensive research, its etiology remains uncertain with genetic, metabolic, environmental factors implicated. This review explores the relationship between PCOS oxidative stress (OS), focusing on molecular pathways their effects physiology. OS arises from an imbalance reactive oxygen species (ROS) production intricate endogenous antioxidant defenses, causing cellular damage. Recent studies show heightened conditions in women, potentially exacerbating hormonal imbalances, inflammation, insulin resistance. The elevated ROS generation, combined diminished defense patients, links to compromised oocyte health, abnormal follicle growth, endometrial issues. Interventions such as supplementation lifestyle alterations promise re-establishing balance, improving symptoms, fertility. consolidates contemporary insights into cross-talk OS, emphasizing prospective treatment importance further explorations elucidate this interconnection. URN:NBN:sciencein.jist.2024.v12.752

Язык: Английский

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

Life, Год журнала: 2023, Номер 13(4), С. 1056 - 1056

Опубликована: Апрель 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

Язык: Английский

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Cellular senescence in the pathogenesis of ovarian dysfunction

Journal of Obstetrics and Gynaecology Research, Год журнала: 2024, Номер 50(5), С. 800 - 808

Опубликована: Фев. 27, 2024

Abstract The follicular microenvironment is crucial for normal ovarian function, and intra‐ovarian factors, in coordination with gonadotropins, contribute to its regulation. Recent research has revealed that the accumulation of senescent cells worsens adverse environment various tissues plays critical roles chronological aging pathological conditions. Cellular senescence involves cell‐cycle arrest, a senescence‐associated secretory phenotype (SASP), macromolecular damage, dysmetabolism. In this review, I summarize latest knowledge regarding role cellular conditions ovary, context reproduction. Specifically, known impair oocyte health cisplatin‐ cyclophosphamide‐induced primary insufficiency pathogenesis polycystic ovary syndrome (PCOS). addition, induced during decline reserve associated aging, endometriosis, psychological stress, obesity, but it remains unclear whether causative these Finally, discuss potential use as novel therapeutic target. modification SASP using senomorphic and/or elimination senolytic represent promising strategies. Further elucidation effects insults on reserve, including well pathologies, PCOS, may facilitate new era reproductive medicine.

Язык: Английский

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Cellular senescence of granulosa cells in the pathogenesis of polycystic ovary syndrome

Molecular Human Reproduction, Год журнала: 2024, Номер 30(5)

Опубликована: Апрель 11, 2024

Abstract Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women reproductive age, but its pathology has not been fully characterized and optimal treatment strategy remains unclear. Cellular senescence a permanent state cell-cycle arrest that can be induced by multiple stresses. Senescent cells contribute to pathogenesis various diseases, owing an alteration secretory profile, termed ‘senescence-associated phenotype’ (SASP), including with respect pro-inflammatory cytokines. Senolytics, class drugs selectively eliminate senescent cells, are now being used clinically, combination dasatinib quercetin (DQ) extensively as senolytic. We aimed investigate whether cellular involved PCOS DQ beneficial effects patients PCOS. obtained ovaries from or without PCOS, established mouse model injecting dehydroepiandrosterone. The expression markers p16INK4a, p21, p53, γH2AX, senescence-associated β-galactosidase SASP-related factor interleukin-6 was significantly higher mice than controls. To evaluate hyperandrogenism on vitro, we stimulated cultured human granulosa (GCs) testosterone treated them DQ. increased testosterone, reduced this increase. improved their morphology. These results indicate occurs Hyperandrogenism causes GCs senolytic reduces accumulation improves ovarian morphology under hyperandrogenism. Thus, might represent novel therapy for

Язык: Английский

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Identification of crucial pathways and genes linked to endoplasmic reticulum stress in PCOS through combined bioinformatic analysis

Frontiers in Molecular Biosciences, Год журнала: 2025, Номер 11

Опубликована: Янв. 9, 2025

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic condition impacting millions of women worldwide. This study sought to identify granulosa cell endoplasmic reticulum stress (GCERS)-related differentially expressed genes (DEGs) between with PCOS those without using bioinformatics investigate the related molecular mechanisms. Two datasets were downloaded from GEO analysed limma package DEGs in two groups-PCOS normal cells. Enrichment analyses, including GO, KEGG, GSEA, then conducted on DEGs. Differential immune infiltration was assessed CIBERSORT correlations biomarkers evaluated. Networks for protein-protein interactions, transcription factor-target genes, miRNA-target drug-target constructed visualized Cytoscape key hub gene nodes. Finally, differential expression correlated. Overall, 127 co-DEGs identified datasets. Our revealed that these primarily associated cycle arrest, p53-mediated signal transduction, drug response, gland development, functions enriched growth factor binding, collagen receptor protein kinase activity. GSEA inflammatory pathways. Eleven genes-MMP9, SPI1, IGF2R, GPBAR1, PDGFA, BMPR1A, LIFR, PRKAA1, MSH2, CDC25C, KCNH2-were through PPI, TF target miRNA networks. We several crucial pathways linked onset development PCOS. findings offer clear connection GCERS, clarify mechanisms driving progression, new perspectives discovering valuable therapeutic targets potential condition.

Язык: Английский

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Ameliorative Effect of Itaconic Acid/IRG1 Against Endoplasmic Reticulum Stress-Induced Necroptosis in Granulosa Cells via PERK-ATF4-AChE Pathway in Bovine

Cells, Год журнала: 2025, Номер 14(6), С. 419 - 419

Опубликована: Март 12, 2025

The necroptosis of granulosa cells has been proven to be one the important triggers follicular atresia, which is an cause reduced reproductive capacity in cows. rapid growth accompanied by endoplasmic reticulum stress (ERS), leading cell death. However, link between ERS and necroptosis, as well its mechanism bovine still unclear. Itaconic acid endogenous anti-inflammatory antioxidant small-molecule compound that can alleviate ERS. Therefore, aim current study evaluate effect on investigate ameliorative itaconic against ERS-induced cells. Bovine were treated with tunicamycin (Tm) induce After addition inhibitor Nec-1 detection inducer acetylcholinesterase (AChE), flow cytometry, transmission electron microscopy, mass spectrometry used analyze expression IRG1 In addition, role PERK pathway downstream was also investigated. We report here supplementation significantly attenuates damage. summary, this research provides a scientific basis drug reference for treating atresia improving capacity.

Язык: Английский

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FTO-mediated m6A modification elevates the MFN2 mRNA stability to suppress ovarian granulosa cell senescence

International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 142181 - 142181

Опубликована: Март 1, 2025

Язык: Английский

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Luteolin mitigates doxorubicin-induced hepatotoxicity and neurotoxicity: modulating the liver–brain axis via IRE1α/GRP78/ATF6 endoplasmic reticulum stress pathways and miRNA-199a-5p expression

Future Journal of Pharmaceutical Sciences, Год журнала: 2025, Номер 11(1)

Опубликована: Апрель 14, 2025

Abstract Background Doxorubicin (DOX) has long been a foundational drug in cancer therapeutics. Despite its proven efficacy, the persistent challenge of mitigating associated side effects, notably hepatotoxicity and neurotoxicity, underscores necessity for intervention. Luteolin (LUT) is naturally derived flavonoid with spectrum bioactive characteristics, involving anti-apoptotic, antioxidant, anti-inflammatory, anti-cancer attributes. This study investigates possible protective effect LUT against DOX-induced focusing on modulation endoplasmic reticulum (ER) stress pathways miRNA 199a- 5p expression. Forty-eight male Sprague Dawley rats were assigned to six groups: control, (200 mg/kg), DOX (3.5 mg/kg, i.p.) administered twice per week 3 weeks, three treatment groups that received daily oral gavage at doses 50, 100, 200 mg/kg weeks alongside DOX. Results Behavioral assessments revealed best improvements co-treated high dose paralleled by mitigation neurodegeneration cortex hippocampal areas brain. The hepatoprotective mg/kg) demonstrated notable decrease liver enzymes restoration hepatocytic architecture, coupled upregulation miRNA-199a-5p suppression glucose-regulated protein 78 (GRP78). inhibited ER via suppressing inositol-requiring enzyme 1 alpha (IRE1α)/protein kinase R-like (PERK)/eukaryotic initiation factor 2 (eIF2α)/activating transcription 6 (ATF6) axes, thereby inhibiting apoptosis. Conclusions efficacious alleviating hepatic injury neurotoxicity dampening pathways. Graphical abstract

Язык: Английский

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The effects of inhibiting IRE1α on the viability of ovarian granulosa cells

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Июнь 4, 2025

IRE1α, a type I transmembrane protein characterized by cytoplasmic serine/threonine kinase domain, is related to ER stress and function maintenance. In this study, 4µ8c, highly effective selective inhibitor of IRE1α RNase, APY29, an ATP competitive inhibitor, inhibiting autophosphorylation the were employed elucidate on proliferation ovarian granulosa cells, with ultimate goal identifying novel strategies methodologies for prevention treatment associated diseases. Human cells (SVOG) cultured in vitro treated inhibitors 4µ8c APY29. It was shown that inhibition reduced cell ability dealing misfolded protein, triggered oxidative stress, altered mitochondrial membrane potential, inflicted DNA damage, eventually lead apoptosis.

Язык: Английский

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Integrated analysis of TCGA data identifies endoplasmic reticulum stress-related lncRNA signature in stomach adenocarcinoma

ONCOLOGIE, Год журнала: 2023, Номер 26(2), С. 221 - 237

Опубликована: Дек. 29, 2023

Abstract Objectives To investigaed the role of endoplasmic reticulum stress (ERS)-related long non-coding RNAs (lncRNAs) in stomach adenocarcinoma (STAD) using TCGA data. Methods This study integrated clinical, transcriptomic, and tumor data from Cancer Genome Atlas (TCGA). The expression ERS genes was evaluated, alongside their association with identified lncRNAs. Gene set enrichment analysis immune cell infiltration were performed to elucidate biological pathways influenced by these Results five lncRNAs – AC012055.1, LINC01235, LINC00571, LINC02073, CFAP61-AS1 strongly correlated cancer prognosis. A prognostic model based on developed validated across low- high-risk groups. Potential associated uncovered through GSEA. Additionally, screening drugs potentially effective against STAD, highlighting co-expressed as probable therapeutic targets. Conclusions research offers detailed insights into molecular mechanisms enhancing understanding potential targets showing promise for clinical applications.

Язык: Английский

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