Neurotransmitter and neuromodulator imbalance in kisspeptin/GnRH regulation in rodent models of polycystic ovary syndrome and its implications for mental health disorders: A systematic review.

IFN-γ-induced AIM2-PANoptosis in granulosa cells leads to ovulatory dysfunction in polycystic ovary syndrome.

To compare bioelectrical impedance analysis (BIA)-derived body composition between women with polycystic ovary syndrome (PCOS) and body mass index (BMI)-matched controls, and to investigate associations with metabolic, hormonal, and inflammatory markers. This cross-sectional study included 35 women with PCOS and 37 BMI-matched healthy controls, aged 18-40 years, with BMI <35 kg/m2. Clinical, anthropometric, metabolic, hormonal, and inflammatory parameters were assessed. Body composition was determined by direct segmental multifrequency BIA, including fat mass (FM), trunk fat mass (trunk FM), lean mass (LM), FM index, fat-to-lean mass ratio (F/L ratio), and trunk-to-peripheral fat ratio. Women with PCOS (28 ± 5.3 years, 26.6 ± 3.6 kg/m2) had higher FM index, trunk FM, and F/L ratio, while LM did not differ. They also showed higher fasting insulin, homeostatic model assessment for insulin resistance (HOMA-IR), glycated hemoglobin type A1c (HbA1c), low-density lipoprotein cholesterol, free androgen index, testosterone, androstenedione, and dehydroepiandrosterone sulfate, and lower sex hormone-binding globulin (SHBG). Among BIA parameters, FM, FM index, and F/L ratio showed more consistent associations with insulin resistance and selected inflammatory markers than trunk FM. In women with PCOS, these measures were positively correlated with fasting insulin and HOMA-IR and inversely correlated with SHBG. Associations with HbA1c and IL-6 were modest and not uniformly observed across all adiposity measures. No significant correlations were found with fasting glucose, HDL-c, triglycerides, or androgen levels. Women with PCOS exhibit higher adiposity, particularly reflected by FM index and F/L ratio, which show closer associations with metabolic and inflammatory dysfunction than trunk FM. These findings support the potential use of BIA as an accessible, low-cost, and noninvasive tool for the cross-sectional assessment of metabolic dysfunction in PCOS. Longitudinal studies are needed to clarify the clinical relevance of these associations.

SESN2 suppresses ferroptosis in polycystic ovary syndrome by maintaining PRDX6 K209 lactylation.

Epigenetic heterogeneity in women with polycystic ovary syndrome.

A distinct plasma lipidomic signature and multi-omics network in depression of polycystic ovary syndrome.

Progress in the treatment of inflammatory diseases with gallic acid and its potential application in gynecological disorders.

Assessment of mycotoxin exposure in women undergoing assisted reproduction: A study of urinary biomarkers related to oocyte and embryo development.

Insulin resistance and related metabolic disorders are becoming increasingly common among women of reproductive age. However, the mechanisms by which insulin signaling influences female fertility remain only partially understood. Currently, there is rapid growth in the use of new insulin-sensitizing medications, such as sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, prescribed to women who may want to conceive, raising concerns about reproductive safety and benefits. Insulin acts at multiple points along the hypothalamic-pituitary-gonadal axis, including ovulatory function, oocyte maturation, and endometrial receptivity. Conditions such as polycystic ovary syndrome, diabetes, or obesity may impair oocyte development, modify IVF success rates, and compromise embryo implantation. Emerging evidence suggests that both SGLT2 inhibitors and GLP-1 receptor agonists improve factors such as ovulatory function and androgen balance, though both carry safety concerns during the periconception period. Clinicians managing women of reproductive age with insulin-related metabolic disorders should incorporate reproductive counseling into treatment planning. Ultimately, fertility-focused trials of newer insulin modifiers may be beneficial.

Mechanisms of reproductive toxicity and endocrine disruption of bisphenols and per- and polyfluoroalkyl substances (PFAS): Implications for women's reproductive health.

Morus alba L. (Sangzhi) alkaloids reduce polycystic ovary syndrome by improving hypothalamic-pituitary-ovarian axis function.

Trilobatin alleviates polycystic ovary syndrome in rats by targeting SIRT2-Mediated PKM2 acetylation in glycolysis and mitochondrial function.

Sustained low-grade inflammation is increasingly recognized as a central element in how polycystic ovary syndrome (PCOS) develops. Here we set out to clarify what role follicular fluid (FF)-borne exosomal miR-424-5p plays in shaping ovarian inflammation and how this ties in with the ovulatory problems seen in PCOS. Across FF samples taken from patients, miR-424-5p levels tracked inversely with pro-inflammatory cytokine concentrations to a striking degree. When granulosa cells (GCs) were challenged with lipopolysaccharide (LPS), delivering exosomal miR-424-5p dampened cytokine release and restored the expression of ovulation-linked genes. Using a dual-luciferase reporter assay, we traced this effect to FGF2, which miR-424-5p binds directly, and we found FGF2/FGFR1 signaling to be conspicuously raised in PCOS. In dehydroepiandrosterone (DHEA)-treated rats modeling the syndrome, giving exosomal miR-424-5p eased ovarian inflammation and brought back part of the lost ovulatory capacity. Taken together, the data suggest that exosomal miR-424-5p tempers ovarian inflammation in PCOS by holding the FGF2/FGFR1 axis in check, which casts fresh light on the follicular abnormalities that mark this condition.

Hereditary PCOS and the environmental toxicant F-53B converge on lipid metabolic reprogramming to impair fetal brain development.

Canagliflozin alleviates hyperandrogen-induced granulosa cell ferroptosis in polycystic ovary syndrome mice by activating the AMPK/GSK3β/NRF2 pathway.

Polycystic ovary syndrome (PCOS) is a common, heterogeneous condition that is tightly linked to obesity, visceral adiposity and insulin resistance. Lifestyle intervention and off-label use of metformin provide only modest and unsustained weight loss, insufficient to reverse obesity-driven pathophysiology in most women with PCOS and obesity. Incretin-based anti-obesity medications, including glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists (dual GIP/GLP-1RAs), offer a biologically plausible way to target adipose dysfunction, hyperinsulinemia and chronic inflammation that drive PCOS in a large subset of patients. In this narrative, product-segmented review, we map the evidence for liraglutide, semaglutide and tirzepatide in PCOS across mechanistic, clinical, and safety domains, and highlight key evidence gaps that limit current practice. Liraglutide has the densest PCOS-specific evidence, demonstrating reproducible weight loss across small and heterogeneous cohorts, reductions in visceral adiposity and hepatic fat, improved glycemia and inflammatory markers, and early signals for androgen and fertility benefits in selected phenotypes. Semaglutide data remain sparse but conceptually rich, demonstrating weight-loss efficacy and mechanistic insights, alongside preliminary signals of increased likelihood of natural conception. Tirzepatide currently has no PCOS-specific evidence and cannot be recommended beyond extrapolation from obesity and diabetes trials. Across all agents, reproductive outcomes, periconceptional and pregnancy safety, adolescent use, long-term cardiovascular-kidney-metabolic trajectories, obstructive sleep apnea, musculoskeletal health and phenotype-stratified response remain major evidence gaps. We propose a multidimensional, metabolic high-risk PCOS phenotype as the most rational current target for incretin therapy, while emphasizing that well-designed, PCOS-specific trials are essential before these drugs can be viewed as PCOS-modifying therapies rather than powerful, but still adjunctive, weight-loss agents.

Wearable molecularly imprinted polymer sweat testosterone sensor for noninvasive auxiliary early-stage polycystic ovary syndrome at rest.

Background: Zearalenone (ZEN) is a mycotoxin that the fungus produces Fusarium spp., which reaches humans through food contaminated with mycotoxins. The purpose of this study is to look into the presence of zearalenone in the serum among females suffering from polycystic ovary syndrome, how it influences the levels of FSH, or follicle-stimulating hormone and estrogen, and how it relates to CYP19 gene polymorphisms. Methodology: This was accomplished by obtaining blood samples from both healthy women and women with polycystic ovarian syndrome and measuring zearalenone, estrogen, and FSH using ELISA. PCR was also employed to examine the CYP19 gene's SNPs utilizing the HSP92ll enzyme. Results: The findings show that the amount of zearalenone in polycystic ovarian syndrome women's serum (4.03 ± 1.65 ng/ml) was greater than the healthy women (0.5 ± 0.1 ng/ml), Additionally, It was noted that samples of women with PCOS had higher levels of estrogen (60.86 ± 18.27 pg/ml) than samples of healthy women (48.82 ± 17.90 pg/ml). In contrast, samples of blood from polycystic ovarian syndrome patients had lower levels of FSH (5.22±1.56 ml.U/ml) than samples from healthy women (7.55±1.73 ml.U/ml). The PCR results using the HSP92ll enzyme indicate the presence of three the genotype AA (homozygosity) AG (heterozygosity) GG (homozygous) The genotypes in women with PCOS indicate that they are GG, AG, AA (38, 43, 19)% compared to healthy women (20, 35, 45)%, respectively, Conclusions: This study indicates the presence of the toxin zearalenone in PCOS-affected women's blood serum. Toxins in the serum contribute to PCOS.

Dysfunctional autophagy in ovarian granulosa cells (GCs) represents a key pathological feature of insulin resistance (IR) in polycystic ovary syndrome (PCOS), though regulatory roles of autophagy-associated lncRNAs remain poorly characterized. Comparing GCs from IR-PCOS patients, non-IR PCOS patients, and non-PCOS controls revealed significantly elevated LUCAT1 expression in IR-PCOS. Functional validation via LUCAT1 knockdown in primary IR-PCOS GCs assessed cell viability, apoptosis, autophagy markers, and insulin sensitivity. Mechanistic studies employed Ago2-RIP, dual-luciferase reporter assays, and rescue experiments with miR-19a-3p mimic or HMGB1 overexpression. LUCAT1 knockdown promoted cell viability, reduced cell apoptosis, suppressed autophagy (decreased LC3B puncta, reduced LC3II/LC3I ratio, elevated p62), enhanced insulin sensitivity (upregulated IRS1, promoted GLUT4 membrane translocation, increased glucose uptake), and restored the secretion of steroid hormones (estradiol and progesterone) in GCs. Mechanistically, LUCAT1 functioned as a molecular sponge for miR-19a-3p, thereby increasing HMGB1 expression. MiR-19a-3p mimic replicated LUCAT1 knockdown effects, while HMGB1 overexpression abolished these phenotypes. Altogether, LUCAT1 knockdown reduces autophagy, apoptosis, dysfunction, and IR of GCs from PCOS-IR patients through modulating the miR-19a-3p/HMGB1 axis. This study is a retrospective observational clinical study. No prospective study-designed interventions, additional clinical treatments, or randomized controlled trials were performed in this work. In accordance with the recommendations of the International Committee of Medical Journal Editors (ICMJE), formal clinical trial registration is not mandatory for retrospective observational studies without trial intervention. Thus, no trial registration number is available for this study.

Infertility is an increasing concern for many women and can affect both physical and emotional well-being. The central nervous system (CNS) - particularly the hypothalamus, pituitary gland, and pineal gland - plays a crucial role in female reproductive health. We conducted a narrative review of relevant studies published between 2015 and 2025, sourcing data from PubMed and Scopus. Our goal was to investigate how dysregulation of hormones from the hypothalamus, pituitary gland, and pineal gland contributes to fertility-related disorders, such as impairments in ovulation, oocyte quality, and embryo development. Both human and significant animal studies were considered to better understand how CNS hormones affect fertility. The findings emphasize the roles of key hormones, including gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), melatonin, adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), and vasopressin (ADH). The proper timing and balance of these hormones are vital. For instance, GnRH pulses regulate the release of LH and FSH, which are essential for ovulation and follicle development. Melatonin supports oocyte health and helps maintain the menstrual cycle, while ACTH and TSH are also involved in reproductive function. Vasopressin affects uterine activity and hormone production. Understanding these hormonal interactions may lead to better diagnostic tools and more effective treatment strategies for conditions such as polycystic ovary syndrome (PCOS) and other fertility-related disorders. Unlike previous studies, this research provides a comprehensive investigation of how CNS-mediated hormonal regulation influences female reproductive outcomes, examining the roles of all involved hormones.