Fat Mass and Obesity-Associated Protein Regulates Granulosa Cell Aging by Targeting Matrix Metalloproteinase-2 Gene Via an N6-Methyladenosine-YT521-B Homology Domain Family Member 2-Dependent Pathway in Aged Mice.

In this study, we aimed to investigate the molecular mechanisms of RNA N6-methyladenosine (m6A) modification and how its associated proteins affect granulosa cell aging. A granulosa cell senescence model was constructed to detect the differences in total RNA m6A modification levels and the expression of related enzymes. Changes in downstream molecular expression and the effects on the cellular senescence phenotype were explored by repeatedly knocking down and overexpressing the key genes fat mass and obesity-associated protein (FTO), YT521-B homology domain family member 2 (YTHDF2), and matrix metalloproteinase-2 (MMP2). There was an increased total RNA m6A modification and decreased expression of the demethylase FTO and target gene MMP2 in senescent granulosa cells. FTO and MMP2 knockdown promoted granulosa cell senescence, whereas FTO and MMP2 overexpression retarded it. YTHDF2 and FTO can bind to the messenger RNA of MMP2. The extracellular signal-regulated kinase (ERK) pathway, which is downstream of MMP2, retarded the process of granulosa cell senescence through ERK activators. In granulosa cells, FTO can regulate the expression of MMP2 in an m6A-YTHDF2-dependent manner, influencing the activation status of the ERK pathway and contributing to the aging process of granulosa cells.

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

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

Ovarian fibrosis: molecular mechanisms and potential therapeutic targets.

Ovarian fibrosis, characterized by the excessive proliferation of ovarian fibroblasts and the accumulation of extracellular matrix (ECM), serves as one of the primary causes of ovarian dysfunction. Despite the critical role of ovarian fibrosis in maintaining the normal physiological function of the mammalian ovaries, research on this condition has been greatly underestimated, which leads to a lack of clinical treatment options for ovarian dysfunction caused by fibrosis. This review synthesizes recent research on the molecular mechanisms of ovarian fibrosis, encompassing TGF-ß, extracellular matrix, inflammation, and other profibrotic factors contributing to abnormal ovarian fibrosis. Additionally, we summarize current treatment approaches for ovarian dysfunction targeting ovarian fibrosis, including antifibrotic drugs, stem cell transplantation, and exosomal therapies. The purpose of this review is to summarize the research progress on ovarian fibrosis and to propose potential therapeutic strategies targeting ovarian fibrosis for the treatment of ovarian dysfunction.

Peroxiredoxin 4 deficiency induces accelerated ovarian aging through destroyed proteostasis in granulosa cells.

Ovarian aging, a complex and challenging concern within the realm of reproductive medicine, is associated with reduced fertility, menopausal symptoms and long-term health risks. Our previous investigation revealed a correlation between Peroxiredoxin 4 (PRDX4) and human ovarian aging. The purpose of this research was to substantiate the protective role of PRDX4 against ovarian aging and elucidate the underlying molecular mechanism in mice. In this study, a Prdx4-/- mouse model was established and it was observed that the deficiency of PRDX4 led to only an accelerated decline of ovarian function in comparison to wild-type (WT) mice. The impaired ovarian function observed in this study can be attributed to an imbalance in protein homeostasis, an exacerbation of endoplasmic reticulum stress (ER stress), and ultimately an increase in apoptosis of granulosa cells. Furthermore, our research reveals a noteworthy decline in the expression of Follicle-stimulating hormone receptor (FSHR) in aging Prdx4-/- mice, especially the functional trimer, due to impaired disulfide bond formation. Contrarily, the overexpression of PRDX4 facilitated the maintenance of protein homeostasis, mitigated ER stress, and consequently elevated E2 levels in a simulated KGN cell aging model. Additionally, the overexpression of PRDX4 restored the expression of the correct spatial conformation of FSHR, the functional trimer. In summary, our research reveals the significant contribution of PRDX4 in delaying ovarian aging, presenting a novel and promising therapeutic target for ovarian aging from the perspective of endoplasmic reticulum protein homeostasis.

Unveiling the role of chronic inflammation in ovarian aging: insights into mechanisms and clinical implications.

Ovarian aging, a natural process in women and various other female mammals as they age, is characterized by a decline in ovarian function and fertility due to a reduction in oocyte reserve and quality. This phenomenon is believed to result from a combination of genetic, hormonal, and environmental factors. While these factors collectively contribute to the shaping of ovarian aging, the substantial impact and intricate interplay of chronic inflammation in this process have been somewhat overlooked in discussions. Chronic inflammation, a prolonged and sustained inflammatory response persisting over an extended period, can exert detrimental effects on tissues and organs. This review delves into the novel hallmark of aging-chronic inflammation-to further emphasize the primary characteristics of ovarian aging. It endeavors to explore not only the clinical symptoms but also the underlying mechanisms associated with this complex process. By shining a spotlight on chronic inflammation, the aim is to broaden our understanding of the multifaceted aspects of ovarian aging and its potential clinical implications.

Age-associated increased stiffness of the ovarian microenvironment impairs follicle development and oocyte quality and rapidly alters follicle gene expression.

In humans, aging triggers cellular and tissue deterioration, and the female reproductive system is the first to show signs of decline. Reproductive aging is associated with decreased ovarian reserve, decreased quality of the remaining oocytes, and decreased production of the ovarian hormones estrogen and progesterone. With aging, both mouse and human ovaries become pro-fibrotic and stiff. However, whether stiffness directly impairs ovarian function, folliculogenesis, and oocyte quality is unknown. To answer this question, we cultured mouse follicles in alginate gels that mimicked the stiffness of reproductively young and old ovaries. Follicles cultured in stiff hydrogels exhibited decreased survival and growth, decreased granulosa cell viability and estradiol synthesis, and decreased oocyte quality. We also observed a reduction in the number of granulosa cell-oocyte transzonal projections. RNA sequencing revealed early changes in the follicle transcriptome in response to stiffness. Follicles cultured in a stiff environment had lower expression of genes related to follicle development and greater expression of genes related to inflammation and extracellular matrix remodeling than follicles cultured in a soft environment. Altogether, our findings suggest that ovarian stiffness directly modulates folliculogenesis and contributes to the progressive decline in oocyte quantity and quality observed in women of advanced maternal age.

Intravascular Laser Blood Irradiation (ILIB) Enhances Antioxidant Activity and Energy Metabolism in Aging Ovaries.

BACKGROUND: Ovarian aging is characterized by the accumulation of free radicals, leading to tissue damage and affecting reproductive health. Intravascular laser irradiation of blood (ILIB, using a low-energy He-Ne laser) is known for its efficacy in treating vascular-related diseases by reducing free radicals and inflammation. However, its impact on ovarian aging remains unexplored. This study aimed to investigate the effects of ILIB on oxidative stress and energy metabolism in aging ovaries. METHODS: Genetic analysis was conducted on 75 infertile patients with aging ovaries, divided into ILIB-treated and control (CTRL) groups. Patients underwent two courses of laser treatment, and clinical parameters were evaluated. Cumulus cells were collected for the genetic analysis of oxeiptosis, glycolysis, and the tricarboxylic acid (TCA) cycle. RESULTS: The analysis of gene expression patterns revealed intriguing findings in ILIB-treated patients compared to the untreated group. Notably, ILIB treatment resulted in significant upregulation of oxeiptosis-related genes AIFM1 and NRF2, suggesting a potential protective effect against oxidative stress-induced cell death. Furthermore, ILIB treatment led to a downregulation of glycolysis-associated gene hexokinase 2 (HK2), indicating a shift away from anaerobic metabolism, along with an increase in PDHA levels, indicative of enhanced mitochondrial function. Consistent with these changes, ILIB-treated patients exhibited elevated expression of the key TCA cycle genes citrate synthase (CS), succinate dehydrogenase complex subunit A (SDHA), and fumarate hydratase (FH), signifying improved energy metabolism. CONCLUSION: The findings from this study underscore the potential of ILIB as a therapeutic strategy for mitigating ovarian aging. By targeting oxidative stress and enhancing energy metabolism, ILIB holds promise for preserving ovarian function and reproductive health in aging individuals. Further research is warranted to elucidate the underlying mechanisms and optimize the application of ILIB in clinical settings, with the ultimate goal of improving fertility outcomes in women experiencing age-related ovarian decline.

Pilot Study on Next-Generation Sequencing Analysis of Vaginal Microbiota in Clinically Infertile Patients Treated with Probiotics.

Background: In this investigation, we aimed to understand the influence of oral probiotic supplementation on the vaginal microbiota of women preparing for assisted reproductive technology (ART) procedures. Given the importance of a healthy microbiome for reproductive success, this study sought to explore how probiotics might alter the bacterial composition in the vaginal environment. Methods: We recruited a cohort of 30 women, averaging 37 years of age (ranging from 31 to 43 years), who were scheduled to undergo ART. Using 16S ribosomal RNA (rRNA) sequencing, we meticulously analyzed the vaginal microbiota composition before and after the administration of oral probiotic supplements. Results: Our analysis identified 17 distinct microorganisms, including 8 species of Lactobacillus. Following probiotic supplementation, we observed subtle yet notable changes in the vaginal microbiota of some participants. Specifically, there was a decrease in Gardnerella abundance by approximately 20%, and increases in Lactobacillus and Bifidobacterium by 10% and 15%, respectively. Additionally, we noted a significant reduction in the Firmicutes/Bacteroidetes (F/B) ratio in the probiotic group, indicating potential shifts in the overall bacterial composition. Conclusions: These preliminary findings suggest that oral probiotic supplementation can induce significant changes in the vaginal microbiota of middle-aged women undergoing ART, potentially improving their overall bacterial profile. Future studies should consider a larger sample size and a narrower age range to validate these results. Investigating factors related to female hormone production could also provide deeper insights. Understanding the effects of probiotics on the vaginal microbiota in patients with ovarian aging may lead to personalized interventions and better reproductive outcomes.

Zuogui Pills alleviate cyclophosphamide-induced ovarian aging by reducing oxidative stress and restoring the stemness of oogonial stem cells through the Nrf2/HO-1 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Zuogui Pill (ZGP) is a traditional herbal formula of Chinese Medicine with a long history of use in alleviating ovarian aging. AIM OF THE STUDY: To examine the impact of ZGP on oxidative stress and the stemness of oogonial stem cells (OSCs) in cyclophosphamide (CTX)-induced ovarian aging, as well as its molecular mechanisms involving the nuclear factor erythroid 2-related factor 2 (Nrf2, NFE2L2)/heme oxygenase-1 (HO-1, Hmox1) pathway. MATERIALS AND METHODS: Female Sprague-Dawley (SD) rats were randomly divided into seven groups: control, model (CTX), estradiol valerate (EV, 0.103 mg/kg), ZGP-L (low dose Zuogui Pill, 1.851 g/kg), ZGP-H (high dose Zuogui Pill, 3.702 g/kg), ML385 (30 mg/kg), and ML385+ZGP-L. After CTX modeling, the EV, ZGP-L, ZGP-H, and ML385+ZGP-L groups were treated by gavage for 8 weeks, while the ML385 and ML385+ZGP-L groups were administered the Nrf2 antagonist ML385 twice a week. OSCs were isolated after modeling and then treated with drug serum containing 10% ZGP or 10 µM ML385. The general conditions of the rats, including body weight, ovarian weight/body weight ratio, and estrous cycle, were observed. Ovarian ultrastructure, follicle and corpus luteum counts were assessed via hematoxylin and eosin (H&E) staining. Serum hormone levels were measured using enzyme-linked immunosorbent assay (ELISA). Nrf2/HO-1 pathway, stem cell, germ cell, and cell cycle biomarkers were analyzed by qPCR and Western blot. Cell viability was assessed by cell counting kit-8 (CCK-8) assay. Oxidative stress biomarkers were evaluated using flow cytometry and assay kits. Immunofluorescence was employed to detect and locate OSCs in the ovary, quantify the average fluorescence intensity, and identify OSCs. RESULTS: After ZGP treatment, rats with CTX-induced ovarian aging exhibited improved general condition, increased body weight, higher total ovarian weight to body weight ratio, and a restoration of the estrous cycle similar to the control group. Serum levels of estradiol (E2) and follicle stimulating hormone (FSH), two sex hormones, were also improved. Ovarian ultrastructure and follicle count at all stages showed improvement. Moreover, the viability and proliferation capacity of OSCs were enhanced following ZGP intervention. The Nrf2/HO-1 pathway was found to be down-regulated in CTX-induced aging ovarian OSCs. However, ZGP reversed this effect by activating the expression of Nrf2, HO-1, and NAD(P)H oxidoreductase 1 (NQO1), increasing the activity of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and reducing the accumulation of malonaldehyde (MDA) and reactive oxygen species (ROS), thus restoring resistance to oxidative stress. Additionally, ZGP improved the cell cycle of OSCs, up-regulated the expression of Cyclin D1 and Cyclin E1, restored cell stemness, promoted proliferation, enhanced the expression of cell stemness markers octamer-binding transcription factor 4 (Oct4) and mouse VASA homolog (MVH), and down-regulated the expression of P21, thereby inhibiting apoptosis. The therapeutic effects of ZGP against oxidative stress and restoration of cell stemness were attenuated following inhibition of the Nrf2 signaling pathway using ML385. CONCLUSIONS: ZGP protected against CTX-induced ovarian aging by restoring normal ovarian function, alleviating oxidative stress in aging OSCs, promoting OSCs proliferation, and restoring their stemness in rats, possibly through regulating the Nrf2/HO-1 pathway.

Ovarian aging: energy metabolism of oocytes.

In women who are getting older, the quantity and quality of their follicles or oocytes and decline. This is characterized by decreased ovarian reserve function (DOR), fewer remaining oocytes, and lower quality oocytes. As more women choose to delay childbirth, the decline in fertility associated with age has become a significant concern for modern women. The decline in oocyte quality is a key indicator of ovarian aging. Many studies suggest that age-related changes in oocyte energy metabolism may impact oocyte quality. Changes in oocyte energy metabolism affect adenosine 5'-triphosphate (ATP) production, but how related products and proteins influence oocyte quality remains largely unknown. This review focuses on oocyte metabolism in age-related ovarian aging and its potential impact on oocyte quality, as well as therapeutic strategies that may partially influence oocyte metabolism. This research aims to enhance our understanding of age-related changes in oocyte energy metabolism, and the identification of biomarkers and treatment methods.

Gut microbiota modulation: a narrative review on a novel strategy for prevention and alleviation of ovarian aging.

The global rise in life expectancy corresponds with a delay in childbearing age among women. Ovaries, seen as the chronometers of female physiological aging, demonstrate features of sped up aging, evidenced by the steady decline in both the quality and quantity of ovarian follicles from birth. The multifaceted pathogenesis of ovarian aging has kindled intensive research interest from the biomedical and pharmaceutical sectors. Novel studies underscore the integral roles of gut microbiota in follicular development, lipid metabolism, and hormonal regulation, forging a nexus with ovarian aging. In this review, we outline the role of gut microbiota in ovarian function (follicular development, oocyte maturation, and ovulation), compile and present gut microbiota alterations associated with age-related ovarian aging. We also discuss potential strategies for alleviating ovarian aging from the perspective of gut microbiota, such as fecal microbiota transplantation and probiotics.

A Molecular Perspective and Role of NAD+ in Ovarian Aging.

The decline in female fecundity is linked to advancing chronological age. The ovarian reserve diminishes in quantity and quality as women age, impacting reproductive efficiency and the aging process in the rest of the body. NAD+ is an essential coenzyme in cellular energy production, metabolism, cell signaling, and survival. It is involved in aging and is linked to various age-related conditions. Hallmarks associated with aging, diseases, and metabolic dysfunctions can significantly affect fertility by disturbing the delicate relationship between energy metabolism and female reproduction. Enzymes such as sirtuins, PARPs, and CD38 play essential roles in NAD+ biology, which actively consume NAD+ in their enzymatic activities. In recent years, NAD+ has gained much attention for its role in aging and age-related diseases like cancer, Alzheimer's, cardiovascular diseases, and neurodegenerative disorders, highlighting its involvement in various pathophysiological processes. However, its impact on female reproduction is not well understood. This review aims to bridge this knowledge gap by comprehensively exploring the complex interplay between NAD+ biology and female reproductive aging and providing valuable information that could help develop plans to improve women's reproductive health and prevent fertility issues.

Examining the Effects of Nutrient Supplementation on Metabolic Pathways via Mitochondrial Ferredoxin in Aging Ovaries.

As women age, oocytes are susceptible to a myriad of dysfunctions, including mitochondrial dysfunction, impaired DNA repair mechanisms, epigenetic alterations, and metabolic disturbances, culminating in reduced fertility rates among older individuals. Ferredoxin (FDX) represents a highly conserved iron-sulfur (Fe-S) protein essential for electron transport across multiple metabolic pathways. Mammalian mitochondria house two distinct ferredoxins, FDX1 and FDX2, which share structural similarities and yet perform unique functions. In our investigation into the regulatory mechanisms governing ovarian aging, we employed a comprehensive multi-omics analysis approach, integrating spatial transcriptomics, single-cell RNA sequencing, human ovarian pathology, and clinical biopsy data. Previous studies have highlighted intricate interactions involving excessive lipid peroxide accumulation, redox-induced metal ion buildup, and alterations in cellular energy metabolism observed in aging cells. Through a multi-omics analysis, we observed a notable decline in the expression of the critical gene FDX1 as ovarian age progressed. This observation prompted speculation regarding FDX1's potential as a promising biomarker for ovarian aging. Following this, we initiated a clinical trial involving 70 patients with aging ovaries. These patients were administered oral nutritional supplements consisting of DHEA, ubiquinol CoQ10, and Cleo-20 T3 for a period of two months to evaluate alterations in energy metabolism regulated by FDX1. Our results demonstrated a significant elevation in FDX1 levels among participants receiving nutritional supplementation. We hypothesize that these nutrients potentiate mitochondrial tricarboxylic acid cycle (TCA) activity or electron transport chain (ETC) efficiency, thereby augmenting FDX1 expression, an essential electron carrier in metabolic pathways, while concurrently mitigating lipid peroxide accumulation and cellular apoptosis. In summary, our findings underscore the potential of nutritional intervention to enhance in vitro fertilization outcomes in senescent cells by bolstering electron transport proteins, thus optimizing energy metabolism and improving oocyte quality in aging women.

Preservation of ovarian function using human pluripotent stem cell-derived mesenchymal progenitor cells.

Ovarian reserve diminishes with age, and older women experience a corresponding shift in sex hormone levels. These changes contribute to an age-dependent decrease in fertility and a decline in overall health. Furthermore, while survival rates following cancer treatment have improved for young female patients, a reduction in ovarian function due to the side effects of such treatments can be difficult to avoid. To date, no effective therapy has been recommended to preserve ovarian health in these patients. Mesenchymal progenitor cells (MPCs) are considered a promising option for cell therapy aimed at maintaining fertility and fecundity. Although MPCs derived from human adult tissues are recognized for their various protective effects against ovarian senescence, they are limited in quantity. Consequently, human pluripotent stem cell-derived MPCs (hPSC-MPCs), which exhibit high proliferative capacity and retain genetic stability during growth, have been utilized to delay reproductive aging. This review highlights the impact of hPSC-MPCs on preserving the functionality of damaged ovaries in female mouse models subjected to chemotherapy and natural aging. It also proposes their potential as a valuable cell source for fertility preservation in women with a variety of diseases.

Effect of intraovarian platelet-rich plasma injection on IVF outcomes in women with poor ovarian response: the PROVA randomized controlled trial.

STUDY QUESTION: Does intraovarian platelet-rich plasma (PRP) injection increase the number of mature oocytes obtained after controlled ovarian stimulation (COS) in young women with poor ovarian response (POR) undergoing IVF? SUMMARY ANSWER: Intraovarian PRP injection procedure does not improve mature oocyte yield after COS in women less than 38 years old with an established IVF history of POR. WHAT IS KNOWN ALREADY: POR is frequently encountered among the infertile population and the number of women seeking infertility treatment related to POR is increasing. Effective treatment options for this patient population to conceive with autologous oocytes are lacking. Case series and cohort studies suggest that intraovarian PRP injection may improve follicular recruitment in women with premature ovarian insufficiency (POI) and POR, yet robust randomized studies have not been performed to date to determine the clinical utility of this intervention. STUDY DESIGN, SIZE, DURATION: This was a multi-center randomized controlled trial (RCT) conducted at university-affiliated reproductive centers in the USA and Turkey, between January 2020 and November 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients who met inclusion criteria (<38 years old, two or more prior cycles with <3 oocytes retrieved; and without single gene disorders, prior ovarian surgery, endometriomas, BMI >35 kg/m2, or severe male factor infertility) were randomized to either the PRP or control group. Patients in both groups subsequently underwent COS, oocyte retrieval, ICSI, preimplantation genetic testing for aneuploidy (PGT-A), and single euploid embryo transfer. Number of metaphase II (MII) oocytes obtained was the primary outcome. Secondary outcomes included ovarian reserve tests (antral follicle count [AFC] and anti-Müllerian hormone [AMH]), blastocyst and euploid blastocyst yields, and sustained implantation. The study was powered to detect a difference of one mature oocyte obtained at oocyte retrieval. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 83 patients met inclusion criteria and were randomized to receive autologous intraovarian PRP injection (n = 41) or to no intervention (n = 42). No significant differences were observed in number of MII oocytes retrieved per cycle (2.8 ± 2.4 vs 3.1 ± 3.3 in PRP vs control, respectively; P = 0.9), blastocysts (1.0 ± 1.3 vs 1.3 ± 2.1, P = 0.8), or euploid blastocysts (0.8 ± 1.1 vs 0.9 ± 1.6; P = 0.5). Similarly, no differences were observed in the likelihood of obtaining at least one euploid blastocyst (45% vs 37%, P = 0.4; relative risk [RR], 95% CI = 0.9, 0.6-1.2) or the rate of sustained implantation (31% vs 29%, P = 0.9; RR 1.0, 0.7-1.3). Posttreatment AFC (7.9 ± 4.5 vs 6.8 ± 4.8, P = 0.3) and AMH (0.99 ± 0.98 vs 0.7 ± 0.6, P = 0.2) were also not different between the groups. LIMITATIONS, REASONS FOR CAUTION: Results from this RCT may not be generalizable to other PRP preparations owing to heterogeneity and lack of standardization. The control groups did not undergo a sham ovarian injection, which would have been relevant had the results shown benefit of PRP injection. Only patients with POR were included in this study, and these results may not be generalizable to more severe diminution of ovarian reserve, as seen with POI. WIDER IMPLICATIONS OF THE FINDINGS: The intraovarian PRP injection procedure does not improve mature oocyte yield or other parameters of IVF outcome in women less than 38 years old with an established IVF history of POR. The results from this study do not support the use of intraovarian PRP injection in this population. STUDY FUNDING/COMPETING INTEREST(S): Departmental funds were used and no external funding was requested for this study. ES is a consultant for and receives grant funding from the Foundation for Embryonic Competence. All other authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov Registry Identifier: NCT04163640. TRIAL REGISTRATION DATE: 15 November 2019. DATE OF FIRST PATIENT'S ENROLMENT: 24 February 2020.

Psychological stressors involved in the pathogenesis of premature ovarian insufficiency and potential intervention measures.

Premature ovarian insufficiency (POI) is a common gynecological endocrine disease, which seriously affects women's physical and mental health and fertility, and its incidence is increasing year by year. With the development of social economy and technology, psychological stressors such as anxiety and depression caused by social, life and environmental factors may be one of the risk factors for POI. We used PubMed to search peer-reviewed original English manuscripts published over the last 10 years to identify established and experimental studies on the relationship between various types of stress and decreased ovarian function. Oxidative stress, follicular atresia, and excessive activation of oocytes, caused by Stress-associated factors may be the main causes of ovarian function damage. This article reviews the relationship between psychological stressors and hypoovarian function and the possible early intervention measures in order to provide new ideas for future clinical treatment and intervention.

The Reproductive Lifespan of Ovarian Follicle.

The functional unit within mammalian ovaries is the ovarian follicle. The development of the ovarian follicle is a lengthy process beginning from the time of embryogenesis, passing through multiple different stages of maturation. The purpose of this review is to describe the most basic events in the journey of ovarian follicle development, discussing the importance of ovarian reserve and highlighting the role of several factors that affect oocyte quality and quantity during aging including hormonal, genetic and epigenetic factors. Novel, promising anti-aging strategies are also discussed.

Towards prolonging ovarian reproductive life: Insights into trace elements homeostasis.

Ovarian aging is marked by a reduction in the quantity and quality of ovarian follicles, leading to a decline in female fertility and ovarian endocrine function. While the biological characteristics of ovarian aging are well-established, the exact mechanisms underlying this process remain elusive. Recent studies underscore the vital role of trace elements (TEs) in maintaining ovarian function. Imbalances in TEs can lead to ovarian aging, characterized by reduced enzyme activity, hormonal imbalances, ovulatory disorders, and decreased fertility. A comprehensive understanding of the relationship between systemic and cellular TEs balance and ovarian aging is critical for developing treatments to delay aging and manage age-related conditions. This review consolidates current insights into TEs homeostasis and its impact on ovarian aging, assesses how altered TEs metabolism affects ovarian aging, and suggests future research directions to prolong ovarian reproductive life. These studies are expected to offer novel approaches for mitigating ovarian aging.

Mitochondrial Venus is more likely to have a lower birthweight.

Assisted reproductive technologies (ART) are associated with a moderately higher risk of preterm birth and low birthweight, but the causes are unknown. A recent study by Mertens et al. reveals a link between being born through ART, ovarian stimulation, and an increased incidence of mitochondrial heteroplasmic variants that correlate with lower birthweight.