Polycystic ovary syndrome (PCOS) and obesity frequently coexist and are strongly associated with anovulation, subfertility, pregnancy complications, and long-term cardiometabolic risk. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), widely used in type 2 diabetes and obesity, are increasingly being considered in women of reproductive age. Growing evidence suggests that these agents may affect both metabolic and reproductive outcomes, raising important questions about their role in PCOS management, preconception care, and pregnancy safety. This narrative, concept-driven review evaluates the role of GLP-1 RAs in women’s reproductive health. Major medical databases were searched for studies published within the past 10 years, with emphasis on randomized controlled trials, large observational cohorts, and systematic reviews. In randomized trials involving women with PCOS, GLP-1 RAs have shown clinically meaningful weight loss, improved insulin resistance, and reduced androgen excess. Several studies also reported improved menstrual regularity, ovulation-related outcomes, and conception rates compared with metformin alone. Emerging preconception data suggest that GLP-1-induced weight reduction may improve readiness for spontaneous conception and assisted reproductive techniques. Human pregnancy exposure data remain limited. Available registry and case-series findings have not shown a clear teratogenic signal, but sample sizes are small. The observational nature of pregnancy safety data also limits causal inference. Additionally, evidence from obesity trials suggests that metabolic benefits may decline after treatment discontinuation due to weight regain, which may affect preconception strategies. Overall, GLP-1 RAs appear promising as adjunctive therapy for women with PCOS and obesity, but current evidence is insufficient to support routine use during pregnancy.
Objective: Aging is commonly associated with a decline in immune function, hormonal imbalances, insomnia, constipation, erectile dysfunction, and general muscle weakness. To address these complex conditions, our study used probiotic therapy. Methods: We investigated the effects of two spore-forming probiotics, Clostridium butyricum and Bacillus coagulans , on health parameters in 126 men aged 48–64 years through a population-based intervention. Results: This intervention notably improved age-related conditions, particularly erectile function (measured by the Erectile Function Scale Index [EFSI]), bowel movement regularity, and sleep quality. Among 35 blood biochemical parameters, 19 showed significant changes post-treatment, including those related to immune response, hormone levels, inflammation, and lipid metabolism. Some blood parameters associated with probiotic treatment were identified using exploratory machine learning analysis. Conclusions: The results suggest that supplementation with Clostridium butyricum and Bacillus coagulans may be associated with improvements in certain age-related health parameters in older men.
Recurrent pregnancy loss, defined as two or more pregnancy losses before 20 weeks of gestation, remains unexplained in nearly 50% of cases despite comprehensive evaluation. It is a multifactorial condition that involves uterine, endocrine, thrombophilic, genetic, environmental, and immunological factors. Increasing evidence supports a role for immune dysregulation, particularly autoimmunity. Human leukocyte antigen polymorphisms have received growing attention as immunogenetic factors that may contribute to recurrent pregnancy loss through modulation of maternal–fetal immune tolerance. This review examines the immunogenetic landscape of recurrent pregnancy loss, with an emphasis on autoimmune disorders and associations between specific human leukocyte antigen polymorphisms and disease risk. These include classical class I human leukocyte antigen polymorphisms (A, B, C), non-classical class I polymorphisms (G, F, E), and class II polymorphisms (DQ, DP, DR). Clarification of these associations may provide insight into immune-mediated pregnancy complications and underscores the need for further research to define the underlying etiology of recurrent pregnancy loss. Such advances may support the development of personalized diagnostic and therapeutic strategies.
Objective: S-sulfhydration of proteins is reported to be an important downstream event in signaling mediated by H 2 S, a crucial endogenous gasotransmitter. However, studies on the role of S-sulfhydrated proteins in the ovaries are limited. In this study, we sought to identify and study the function and mechanism of S-sulfhydration of histone variant H3.3 (sH3.3) in mouse granulosa cells. Methods: The levels of sH3.3, indicated enzymes and H 2 S in the primary granulosa cells or KGN cell line The Biotin-HPDP switch, western blotting and Endogenous H 2 S determination were performed to determine. Ovary tissues and serum were collected from the H3f3b C111S mutant and wildtype control mice. RT-PCR, immunofluorescence, IHC assay, western blotting, TUNEL, MDA, and ROS assays were employed to determine the function of sH3.3. The Co-immunoprecipitation (Co-IP), Electrophoretic mobility shift, and Luciferase reporter assays were used to the working mechanism of the sH3.3. Results: Using the mouse model, we showed that sH3.3 deficiency led to female infertility due to ovarian dysfunction. Biological processes, including cell adhesion, steroid biosynthesis, and vascular remodeling, were impaired. Furthermore, we found that sH3.3 deficiency led to reduced ovarian antioxidant capacity. Mechanistically, we demonstrated that sH3.3 deficiency disrupted the interaction with E2F transcription factor 1, which further impaired binding to the Adam19 (a disintegrin and metalloprotease 19) promoter, resulting in reduced Adam19 expression. The subsequent reduction in integrin subunit β1 (ITGB1) shedding led to impairment of the integrin-FAK-ERK1/2 signaling axis, which is critical in granulosa cells. Conclusion: Collectively, our findings reveal a critical role of S-sulfhydration of H3.3 in the ovary for the first time. sH3.3-mediated transcriptional regulation identifies a new mechanism of H 2 S action in mouse granulosa cells.
Endometriosis is a multifactorial disease characterized by the presence of endometrial-like tissue outside the uterus, leading to chronic pain and infertility. Its pathophysiology involves complex interactions between immune dysfunction, genetic and epigenetic alterations, hormonal imbalance, oxidative stress, and microbiota dysbiosis, which drive inflammation and ectopic tissue growth. Understanding these mechanisms is essential for identifying potential biomarkers and developing effective therapeutic strategies. This narrative review synthesizes evidence from 105 English-language studies published between 2012 and 2025 and identified through searches in PubMed, Scopus, MEDLINE, and Google Scholar using Medical Subject Headings terms and Boolean operators. Findings were grouped into five domains: immune dysfunction, genetic and epigenetic factors, oxidative stress, hormone dysregulation, and microbiota. Immune alterations contribute to chronic inflammation, lesion persistence, and oxidative stress. Genetic and epigenetic changes, including DNA methylation and microRNA dysregulation, affect hormonal regulation. Circulating cell-free DNA has emerged as a promising diagnostic biomarker, and the microbiota modulates immune responses and oxidative stress, influencing disease progression. Integrating these domains provides a comprehensive framework for understanding endometriosis and highlights opportunities for biomarker development and novel therapies. Advances in diagnostic tools and targeted interventions may improve early detection, reduce recurrence, support fertility preservation, and facilitate personalized management of the disease.
Objective: Testosterone influences urogenital development during embryogenesis and metabolic–cardiovascular homeostasis in adult women. Observational links between testosterone abnormalities and cardiovascular disease (CVD) are inconclusive due to confounding and reverse causation. We aimed to assess the genetically predicted associations of endogenous sex hormones with CVD risk in women and to explore potential gut microbiota involvement. Methods: Two-sample Mendelian randomization (MR) was conducted to assess associations of bioavailable testosterone (BioT), total testosterone (TotalT), free testosterone (FreeT), and estradiol levels with seven prespecified cardiovascular outcomes. Instruments were derived from published genome-wide association studies (GWASs) in women of European ancestry (sample sizes: 158,089–188,507). Inverse-variance weighted (IVW) MR was the primary approach, complemented by MR-Egger, weighted median, and sensitivity analyses. Two-step mediation MR and multivariable MR (MVMR) were performed using GWAS data on 119 gut microbial genera to explore microbiome-related pathways. Genetic correlations were estimated using linkage disequilibrium score regression (LDSC). Results: Higher BioT levels were associated with lower risks of CVD (OR = 0.935, p = 0.034) and coronary heart disease (CHD; OR = 0.886, p = 0.009). TotalT levels were inversely associated with CVD (OR = 0.949, p = 0.039), and FreeT levels with CHD (OR = 0.940, p = 0.043). Mediation MR and MVMR analyses suggested partial microbiome involvement: Haemophilus mediated 10.6% of the TotalT–CVD association, and Holdemanella mediated 10.1% of the BioT–CVD association. LDSC revealed significant negative genetic correlations of BioT levels with CHD and CVD (all p < 1 × 10 -5 ) and of TotalT and FreeT levels with secondary right heart disease ( p < 0.05). Estradiol levels were not significantly associated with the studied cardiovascular outcomes. Conclusion: Genetically predicted testosterone-related traits showed inverse associations with CVD risk in women and evidence of shared genetic architecture with several cardiovascular outcomes. Exploratory mediation analyses suggested that the gut microbiome may partly mediate these relationships, warranting further validation.
Objective: Maternal and neonatal health remains a global health priority, with persistent disparities in outcomes across regions and socioeconomic groups. We aim to assess current conditions and future projections in maternal and neonatal health worldwide. Methods: This study used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021. It included estimates of incidence, mortality, and disability-adjusted life years (DALYs) for six maternal disorders and four neonatal disorders across 204 countries and territories from 1990 to 2021. Trends were analyzed using an Auto Regressive Integrated Moving Average model to project outcomes to 2050. Results: From 1990 to 2021, most maternal disorders showed a declining trend in incidence, except for maternal hypertensive disorders, which increased by 15.2% (95% uncertainty interval [UI]: 8.1%, 21.0%). Maternal abortion and miscarriage showed the largest decline, with a 17.9% reduction in incidence (95% UI: -23.0%, -11.5%). Hemolytic disease and jaundice showed substantial decreases of 62.1% (95% UI: -63.8%, -59.6%) in males and 59.8% (95% UI: -62.7%, -59.1%) in females. While DALYs associated with most maternal disorders declined, DALYs for ectopic pregnancy increased by 37.8% (95% UI: 13.6%, 67.8%). Projections indicate that by 2050, DALYs for most disorders will continue to decrease, except for ectopic pregnancy, which is expected to rise by 471.04 (95% UI: 125.33 to 1770.39 thousand). Age-specific trends showed a shift in maternal disorder burden toward older age groups. Countries also displayed notable variation in maternal and neonatal disorder DALYs. Conclusions: Maternal and neonatal disorders continue to require global attention. Although the overall disease burden has decreased, progress is limited by rising burdens of hypertensive disorders and ectopic pregnancy, together with persistent geographic inequities. Targeted interventions and strengthened global collaboration are needed to reduce these disparities and promote health equity.
Objective: To investigate the awareness, acceptance, and user experience of self-sampling for high-risk human papillomavirus (HPV) E6/E7 mRNA detection among Chinese women, and to explore its feasibility for integration into cervical cancer screening programs. Methods: A multi-center cross-sectional questionnaire survey was conducted across five hospitals in China from March 2023 to April 2024 among women participating in a related accuracy study. A total of 809 eligible women were recruited, and 737 completed questionnaires were included in the analysis (effective response rate: 97.62%). The self-administered questionnaire assessed demographic characteristics, awareness of cervical cancer screening, acceptance of self-sampling (including preferences, concerns, motivations, and willingness to pay), and user experience. Statistical analyses involved chi-square or non-parametric tests to examine associations between key demographic factors (age, education, and monthly income) and outcomes of interest. Results: The participants were predominantly aged 30–45 years (57.94%), with 46.67% holding a bachelor's degree or above. Awareness of screening was high, with 78.02% having undergone a gynecological examination within the past year. Acceptance of self-sampling was high: 95.93% were willing to use it, 93.49% found the process comfortable, and 99.19% reported understanding of the instructional materials. However, demographic factors significantly influenced perceptions. Higher education and income levels were associated with greater willingness to pay and a stronger emphasis on privacy as a motivation. In contrast, individuals with lower education and income levels reported more concerns about difficulty performing the sampling procedure and were more likely to rely on hospital-based health education for information. Key concerns included test reliability (22.39%) and sampling safety (21.71%). Conclusion: Self-sampling for cervical cancer screening using HPV E6/E7 mRNA testing is highly acceptable among urban Chinese outpatients and is valued for its convenience and privacy. However, acceptance varies significantly by age, education, and income, underscoring the need for population-specific implementation strategies to ensure equitable screening access. The clinical trial registration number is: Chinese Clinical Trial Registry (ChiCTR2200056212).
Turner syndrome, caused by complete or partial monosomy X, leads to gonadal dysgenesis and accelerated follicular atresia, resulting in premature ovarian insufficiency in over 95% of affected individuals. Ovarian tissue cryopreservation (OTC) has emerged as a potential fertility preservation strategy, particularly for prepubertal girls ineligible for ovarian stimulation. Predictors of residual fertility include mosaic karyotype, higher anti-Müllerian hormone and inhibin B levels, lower FSH, evidence of pubertal development, and ultrasonographically visible ovaries, though cryptic gonadal mosaicism may obscure true reproductive potential. While donor oocyte IVF remains the most effective route to pregnancy, autologous oocyte cryopreservation is feasible in selected postpubertal patients, and OTC offers the advantage of earlier intervention without requiring hormonal stimulation. The procedure involves laparoscopic oophorectomy, cortical tissue preparation, cryopreservation, and subsequent reimplantation, with the possibility of preserving not only fertility but also endocrine function and natural pubertal development. However, ovarian tissue in Turner syndrome frequently demonstrates poor follicular morphology and reduced reserve, and significant limitations remain, including premature follicular depletion, technical challenges in tissue processing, suboptimal revascularization after transplantation, and uncertain functional restoration. Psychological and ethical considerations further complicate decision-making, particularly in young patients. Prospective studies such as Turner Fertility support procedural feasibility, yet live birth outcomes remain rare. Overall, OTC may represent a meaningful fertility preservation option in carefully selected individuals with Turner syndrome, but current evidence is limited and individualized, multidisciplinary counselling is essential to align interventions with realistic expectations.
Objective: Anxiety disorders are more prevalent among women, but the relationship between reproductive factors and anxiety risk remains inadequately explored. Therefore, this study evaluated the associations of reproductive factors—namely, age at first birth (AFB), age at last birth (ALB), number of live births (NLB), and number of pregnancies—with anxiety risk among women to provide evidence for the development of targeted interventions and improvement of mental health outcomes. Methods: Using data from 4,761 female participants in the National Health and Nutrition Examination Survey (NHANES 2007–2012), we conducted multivariable-adjusted logistic regression to assess associations of AFB, ALB, NLB, and number of pregnancies with anxiety. Anxiety symptoms were assessed using the Health-Related Quality Of Life questionnaire. To explore potential effect modification, further analyses stratified by age, hysterectomy status, female hormone use, and race were performed. Results: A significant inverse linear dose-response relationship was observed between AFB and anxiety ( P for trend < 0.001). Specifically, women with an AFB between 21 and 32 years exhibited reduced odds of anxiety compared with those with an AFB <18 years. Multiparous women (≥5 vs ≤2 pregnancies) had a higher anxiety risk after adjustment for age and race (OR = 1.397, P = 0.003). Stratified analyses revealed significant age-dependent associations between an older ALB and anxiety risk ( P for interaction = 0.036). Notably, an older ALB was associated with increased anxiety risk among women aged 45 years or older compared with women aged <18 years. Conclusion: These findings highlight the potential importance of AFB, particularly 21–32 years, in relation to anxiety symptoms, indicating that reproductive timing is associated with anxiety risk.
