TRIM28-Mediated Excessive Oxidative Stress Induces Cellular Senescence in Granulosa Cells and Contributes to Premature Ovarian Insufficiency In Vitro and In Vivo

Antioxidants, Год журнала: 2024, Номер 13(3), С. 308 - 308

Опубликована: Март 1, 2024

Premature ovarian insufficiency (POI) is a clinical syndrome of dysfunction characterized by the abnormal alteration hormone levels such as FSH and E2. POI causes infertility, severe daily life disturbances, long-term health risks. However, underlying mechanism remains largely unknown. In this study, we found that associated with cellular senescence granulosa cells, TRIM28 mediates oxidative stress (OS)-induced in cells. Mechanistically, OS decrease protein KGN Subsequently, it triggers an increase autophagy marker proteins ATG5 LC3B-II, downregulation P62. Abnormal induces markers γ-H2A.X, P16, P21, provoking vitro. The overexpression through microinjection lentivirus attenuated autophagy, senescence, follicular atresia ovaries mice improved mouse fertility vivo. Our study highlights for POI, where reduction TRIM28, which regulated reactive oxygen species, via triggering inducing cell senescence. Shedding light on may represent potential intervention strategy POI.

Язык: Английский

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Human mesenchymal stem cells derived exosomes improve ovarian function in chemotherapy-induced premature ovarian insufficiency mice by inhibiting ferroptosis through Nrf2/GPX4 pathway

Journal of Ovarian Research, Год журнала: 2024, Номер 17(1)

Опубликована: Апрель 15, 2024

Abstract Background Chemotherapy exposure has become a main cause of premature ovarian insufficiency (POI). This study aimed to evaluate the role and molecular mechanism human umbilical cord mesenchymal stem cell-derived exosomes (hUMSC-Exos) in function protection after chemotherapy. Methods hUMSC-Exos were applied cyclophosphamide-induced mice granulosa tumor cells (KGN) determine their effects on follicular development cell apoptosis. Evaluation was done for iron ion reactive oxygen species (ROS) production, lipid peroxidation levels, changes death-related molecules (nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Glutathione Peroxidase enzyme 4 (GPX4), Solute carrier family 7 member 11 cystine glutamate transporter (SLC7A11; xCT)). Furthermore, rescue experiments using an Nrf2 inhibitor performed assess therapeutic cells. Results promoted hormone levels primary follicle POI reduced After treatment, ROS free ions decreased, death marker proteins Nrf2, xCT GPX4 also decreased. ML385 significantly attenuated Conclusion inhibit ferroptosis protect against CTX-induced damage apoptosis through Nrf2/GPX4 signaling pathway, revealing novel therapy.

Язык: Английский

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M6A demethylase FTO-stabilized exosomal circBRCA1 alleviates oxidative stress-induced granulosa cell damage via the miR-642a-5p/FOXO1 axis

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Июнь 25, 2024

Abstract Background Premature ovarian insufficiency (POI) is an important cause of female infertility and seriously impacts the physical psychological health patients. Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exs, H-Exs) have exhibited protective effects on function with unclear mechanisms. Methods A comprehensive analysis Gene Expression Omnibus (GEO) database were used to identify POI-associated circRNAs miRNAs. The relationship between HucMSC-derived exosomal circBRCA1/miR-642a-5p/FOXO1 axis POI was examined by RT-qPCR, Western blotting, reactive oxygen species (ROS) staining, senescence-associated β-gal (SA-β-gal) JC-1 TEM, consumption rate (OCR) measurements ATP assay in vivo vitro . RT-qPCR detected expression circBRCA1 GCs serum patients normal reserve (n = 50) 50); then, correlation indexes analyzed. Results Herein, we found that decreased granulosa cells (GCs) associated reserve. H-Exs improved disorder estrous cycles reproductive hormone levels, reduced number atretic follicles, alleviated apoptosis senescence rats POI. Moreover, mitigated mitochondrial damage reversed induced oxidative stress GCs. Mechanistically, FTO served as eraser increase stability mediating m 6 demethylation circBRCA1, sponged miR-642a-5p block its interaction FOXO1. CircBRCA1 aggravated dysfunction, mimicking or FOXO1 depletion effects, which counteracted inhibition. Conclusion secreted regulated modification, directly upregulate FOXO1, resisted injuries protected Exosomal supplementation may be a general prospect for prevention treatment Graphical

Язык: Английский

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Reproductive Ageing: Inflammation, immune cells, and cellular senescence in the aging ovary

Reproduction, Год журнала: 2024, Номер 168(2)

Опубликована: Май 13, 2024

In brief Recent reports suggest a relationship between ovarian inflammation and functional declines, although it remains unresolved if is the cause or consequence of aging. this review, we compile available literature in area point to several current knowledge gaps that should be addressed through future studies. Abstract Ovarian aging results reduced fertility, disrupted endocrine signaling, an increased burden chronic diseases. The factors contributing natural decline follicles throughout reproductive life are not fully understood. Nevertheless, local may play important role driving Inflammation progressively rises aged ovaries during window, potentially affecting fertility. addition inflammatory markers, recent studies show accumulation specific immune cell populations ovaries, particularly lymphocytes. Other hallmarks ovary include formation multinucleated giant cells, collagen deposition, markers cellular senescence. Collectively, these changes significantly impact quantity quality oocytes. This review explores on alterations associated with inflammation, fibrosis, senescence, cells ovary.

Язык: Английский

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Targeting mitochondria for ovarian aging: new insights into mechanisms and therapeutic potential

Frontiers in Endocrinology, Год журнала: 2024, Номер 15

Опубликована: Июнь 17, 2024

Ovarian aging is a complex process characterized by decline in oocyte quantity and quality, directly impacting fertility overall well-being. Recent researches have identified mitochondria as pivotal players the of ovaries, influencing various hallmarks pathways governing this intricate process. In review, we discuss multifaceted role determining ovarian fate, outline mechanisms through which contribute to aging. Specifically, emphasize potential targeting mitochondrial dysfunction innovative therapeutic approaches, including antioxidants, metabolic improvement, biogenesis promotion, mitophagy enhancement, transfer, traditional Chinese medicine. These strategies hold promise effective means mitigate age-related preserve health. Drawing insights from advanced field, review provides deeper understanding interplay between function aging, offering valuable perspectives for development novel interventions aimed at preserving enhancing reproductive

Язык: Английский

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Baicalin enhances proliferation and reduces inflammatory-oxidative stress effect in H2O2-induced granulosa cells apoptosis via USP48 protein regulation

BMC Complementary Medicine and Therapies, Год журнала: 2024, Номер 24(1)

Опубликована: Янв. 20, 2024

Язык: Английский

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Improving Granulosa Cell Function in Premature Ovarian Failure with Umbilical Cord Mesenchymal Stromal Cell Exosome-Derived hsa_circ_0002021

Tissue Engineering and Regenerative Medicine, Год журнала: 2024, Номер 21(6), С. 897 - 914

Опубликована: Июнь 6, 2024

Язык: Английский

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Bisphenol A and bisphenol AF co-exposure induced apoptosis of human ovarian granulosa cells via mitochondrial dysfunction

Food and Chemical Toxicology, Год журнала: 2024, Номер 191, С. 114894 - 114894

Опубликована: Июль 27, 2024

Язык: Английский

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Exploration of the mechanism and therapy of ovarian aging by targeting cellular senescence

Life Medicine, Год журнала: 2025, Номер 4(1)

Опубликована: Янв. 23, 2025

The ovary is a crucial gonadal organ that supports female reproductive and endocrine functions. Ovarian aging can result in decreased fertility dysfunction across multiple organs. Research has demonstrated cellular senescence various cell types within the trigger decline ovarian function through distinct stress responses, resulting aging. This review explores how may contribute to failure. Additionally, we discuss factors cause senescence, including accumulation of advanced glycation end products, oxidative stress, mitochondrial dysfunction, DNA damage, telomere shortening, exposure chemotherapy. Furthermore, six types, oocytes, granulosa cells, theca immune surface epithelium, endothelial inside explore their contribution accelerated Lastly, describe potential senotherapeutics for treatment offer novel strategies longevity.

Язык: Английский

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Lifestyle Management in Menopause: A Systematic Review of Women With Premature Ovarian Insufficiency

Clinical Endocrinology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 24, 2025

ABSTRACT Objective Premature ovarian insufficiency (POI), the loss of function before age 40, increases risk cardiovascular disease, low bone mineral density, dementia and psychological distress. Lifestyle interventions reduce chronic disease in other populations and, with hormone therapy, may improve health outcomes POI. This review aims to identify role lifestyle, including diet physical activity, managing symptoms, improving quality life (QoL) preventing women The findings this informed 2024 update ESHRE Evidence‐Based POI Guideline. Design A systematic search was conducted PubMed Medline databases from January 2014 February 2024. included randomized controlled trials quasi‐experimental that examined impact lifestyle on Outcomes menopause QoL, health. Risk bias assessed using Joanna Briggs Institute critical appraisal tool. Results literature yielded 890 citations, one study meeting inclusion criteria. Two additional studies guideline chapter searches were included, totalling three articles. involved cancer survivors those Turner syndrome. Limited evidence suggests interventions, particularly density effect dietary supplementation mixed. Conclusions While a healthy is proven prevent diseases QoL postmenopausal women, there limited specific Targeted are needed determine most effective for addressing their heightened risks unmet needs.

Язык: Английский

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