Women with polycystic ovary syndrome (PCOS) exhibit a substantially increased risk of miscarriage, yet the underlying mechanisms remain inadequately understood. This study aimed to investigate whether specific gut microbial dysbiosis and metabolic disturbance are associated with and may potentially contribute to endometrial dysfunction and adverse pregnancy outcomes in women with PCOS. Prospective cohort study integrated with mechanistic experiments. Women's Hospital, School of Medicine, Zhejiang University, China (2022-2024). A total of 110 women with PCOS and 110 age- and body mass index-matched controls were enrolled. We performed 16S rRNA and metagenomic sequencing of gut microbiota, with untargeted and targeted serum metabolomics. Functional validation was conducted using primary human endometrial stromal cells and a PCOS rat model intervened with Parabacteroides merdae (P. merdae) supplementation or faecal microbiota transplantation. Gut microbiota composition, serum metabolites, endometrial senescence markers, and pregnancy outcomes. Women with PCOS exhibited significantly higher miscarriage rates than controls, accompanied by a marked depletion of P. merdae abundance and elevated serum levels of branched-chain amino acids, particularly isoleucine. Exogenous isoleucine induced cellular senescence in human endometrial stromal cells in a dose-dependent manner. Restoration of P. merdae levels in the PCOS rat model resulted in decreased serum isoleucine levels, amelioration of the senescent endometrial phenotype, and reduction in the fetal resorption rate. These findings suggest that P. merdae depletion and the concurrent accumulation of isoleucine may be associated with endometrial senescence and elevated risk of miscarriage, suggesting the possible involvement of a gut microbiota-metabolite pathway in PCOS-related reproductive dysfunction. These results also provide a mechanistic basis for future translational investigations.

This study evaluated the therapeutic potential of lupeol (LUP), a naturally occurring pentacyclic triterpenoid isolated from Ochrosia elliptica (Labill)., in a rat model of letrozole-induced polycystic ovary syndrome (PCOS). Thirty-five adults female Wistar rats were randomly allocated into five groups: normal control, PCOS model, clomiphene citrate-treated (1mg/kg), and two LUP-treated groups (10 and 20mg/kg). Following PCOS induction, treatments were administered orally for 28 consecutive days. PCOS rats exhibited significantly elevated MDA levels and reduced SOD and CAT activities, indicating severe oxidative stress. Lupeol treatment significantly attenuated lipid peroxidation and enhanced SOD activity. However, the increase in CAT activity did not reach statistical significance compared with the PCOS group. Hormonal analysis showed that both lupeol and clomiphene citrate significantly reduced the high LH and testosterone levels in the PCOS group. Lupeol demonstrated a dose-dependent response, lowering testosterone by 22% at 15mg/kg and 27.9% at 30mg/kg At the molecular level, quantitative real-time PCR analysis showed that PCOS was associated with upregulation of steroiFdogenic genes (Cyp17a1 and Hsp3β) and downregulation of the antioxidant regulator Nrf2 and aromatase gene Cyp19a1. These dysregulated gene expression patterns were markedly ameliorated by LUP treatment. Histopathological evaluation revealed multiple enlarged cystic follicles with diminished corpora lutea in PCOS ovaries, whereas LUP administration substantially improved folliculogenesis and luteal development. Immunohistochemical analysis further demonstrated elevated caspase-3 expression in granulosa cells of PCOS ovaries, which was significantly suppressed by LUP in a dose-dependent manner. Collectively, these findings indicate that lupeol exerts potent antioxidant, anti-apoptotic, and hormone-modulatory effects, highlighting its promise as a novel phytotherapeutic candidate for the management of polycystic ovary syndrome.

Kaempferol ameliorates PCOS by alleviating metabolic and endocrine abnormalities as well as oxidative stress.

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.

Polycystic ovary syndrome (PCOS), is a common endocrine disorder associated with chronic inflammation, affecting reproductive health in women. Chronic inflammation is a core driver of PCOS, highlighting the urgent need for interventions that target the underlying inflammatory pathogenesis of PCOS. Sheep placenta extract (SPE), as a traditional medicinal substance with multiple biological effects, including anti-inflammation, has been suggested to offer potential therapeutic benefits in managing chronic inflammation associated with PCOS. Treg dysfunction has emerged as a critical role in many diseases related to chronic inflammation. However, the role of SPE and its anti-inflammation mechanisms related to Treg in PCOS remains underexplored. The gut microbiota (GM) exerts a pivotal role in the pathogenesis and progression of numerous inflammatory disorders. Accordingly, further research is needed to investigate how SPE influences the gut microbial composition. The PCOS model was induced in rats using letrozole, and the animals were then administered SPE. Inflammatory cytokine, sex steroid hormone levels, markers of metabolic, transcriptomics, and 16S rRNA sequencing were assessed. SPE significantly alleviated abnormal ovarian histopathology in PCOS rats. SPE treatment suppressed inflammation by upregulating regulatory T cells (Tregs), with their anti-inflammatory effect mediated through the ERβ-TGFβ1-Smad3 signaling pathway. SPE may ameliorate pathological damage in ovarian tissue of PCOS rats by exerting anti-inflammatory effects through the estrogen receptor β (ERβ)/regulatory T cell (Treg) axis mediated by TGF-β1/Smad3 signaling, alonged with rectifying gut dysbiosis. Further study will focus on the proteomics strategy for identifying SPE, larger-scale validation of samples and comparisons with metformin or GLP-1 receptor agonists.

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder associated with insulin resistance, hyperandrogenism, and infertility. Gut microbiota dysbiosis is suspected to play a significant role in the pathogenesis of PCOS through the gut-brain-gonad axis, an axis that remains incompletely understood. This study aims to evaluate the role of gut microbiota dysbiosis in the mechanism of PCOS with insulin resistance by analyzing the abundance of Lactobacillus sp., levels of Zonulin, Short Chain Fatty Acids (SCFAs), Insulin-Like Growth Factor-1 (IGF-1), and ovarian follicle count in a rat model of PCOS with insuline resistance, which in this study devided into 2 groups, control and treatment group, consist of 20 rats each. This experimental study employed an SEM-PLS approach to assess the relationships among microbiota, inflammation, metabolism, and ovarian function variables in an insulin-resistant PCOS rat model with insulin resistance. The results showed decreases in Lactobacillus sp., SCFAs, and ovarian follicle counts, along with an increase in IGF-1 levels in PCOS model rats. The study, utilizing an insulin-resistant Polycystic Ovary Syndrome (PCOS) rat model, established a strong, statistically significant link between gut microbiota dysbiosis and endocrine/ metabolic dysfunction. These were observed through increased levels of key markers: Zonulin (Control: 3.775, Treatment: 5.545), HOMA-IR (Control: 78.3400, Treatment: 140.9760), and IGF-1 (Control: 141.9665, Treatment: 189.5700). The Structural Equation Modeling (SEM) analysis confirmed two primary pathogenic pathways: (1) Gut Microbe/Metabolite Pathway: A reduction in beneficial Lactobacillus sp. was linked to lower SCFA levels, which influenced IGF-1 and negatively affected ovarian follicle development; (2) Inflammation/Insulin Resistance Pathway: The model established a statistically significant cascade where PCOS induction was strongly associated with Zonulin (β = -0.717), which then positively predicted HOMA-IR (β = 0.630), and HOMA-IR, in turn, strongly predicted IGF-1 (β = 0.662), defining the mechanism as PCOS → Zonulin → HOMA-IR → IGF-1. The dysbiosis mechanism involving gut microbiota in this study's model includes PCOS, Zonulin, HOMA-IR, and IGF-1, as these variables demonstrated statistically significant relationships.

Qingfudaotan Formula (QFDT) is a classical traditional Chinese medicine (TCM) compound used for polycystic ovary syndrome (PCOS), yet its underlying mechanisms remain unclear. This study aimed to elucidate the pharmacological mechanism of QFDT in alleviating PCOS. Active ingredients and targets of QFDT, along with PCOS-associated genes, were retrieved from public databases. Protein-protein interaction (PPI) network analysis, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were employed. Core targets and active ingredients were further validated via molecular docking. A PCOS rat model was utilized for experimental verification. QFDT identified 62 potential PCOS targets, with PPI analysis pinpointing 12 core targets (e.g., AKT1, NFKB1). GO/KEGG enrichment implicated insulin resistance and NF-κB pathways. Molecular docking predicted strong binding (≤-5 kcal/mol) for 5 active ingredients to 5 key targets. In PCOS rats, QFDT significantly reduced body weight and cystic follicles and restored estrous cycles. It notably lowered HOMA-IR (QFDT-H, P<0.05), upregulated ovarian P-PI3K/PI3K and P-AKT/AKT ratios (QFDT-H, P<0.05), and downregulated TLR4/MyD88/p-NFκB, alongside inflammatory markers (LPS, IL-6, TNF-α, etc., QFDT-H, P<0.05). Chronic low-grade inflammation and insulin resistance play critically important roles in the pathogenesis of PCOS. This study demonstrates that QFDT, as a traditional Chinese herbal formula, alleviates PCOS by ameliorating insulin resistance via the PI3K/AKT pathway and suppressing inflammation through the TLR4/NF-κB pathway. This study identified targets for QFDT in PCOS treatment, helping elucidate the mechanisms of action of this ingredient and its potential clinical applications.

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder characterized by hyperandrogenism, ovulatory dysfunction, and the formation of ovarian cysts. Key contributors to its pathophysiology include oxidative stress, inflammation, and altered intracellular signaling, especially within the PI3K/pAKT/PTEN pathway. Galangin, a dietary flavonoid derived from Alpinia galanga, exhibits antioxidant, anti-inflammatory, and estrogen- modulatory properties. This study investigated the protective effects of galangin in a PCOS rat model induced by letrozole and explored its underlying molecular mechanisms. Thirty-six adult female Wistar rats were divided into six groups: control, galangin (8mg/kg), letrozole (1mg/kg), letrozole + galangin (4 or 8mg/kg), and letrozole + metformin (20mg/kg). All treatments were administered orally for 21days. Serum hormones, oxidative stress biomarkers, inflammatory mediators, and key proteins in the PI3K/pAKT/PTEN pathway were assessed, along with histopathological and immunohistochemical analyses. Letrozole administration induced characteristic PCOS-like features, including cystic follicle formation, hormonal imblanaces, oxidative stress, inflammation, and suppression of PI3K/pAKT signaling, accompanied by an increase in PTEN levels. Galangin pretreatment improved ovarian morphology, restored hormonal balance, reduced oxidative and inflammatory responses, and reactivated PI3K/pAKT signaling while downregulating PTEN. These effects were comparable to those observed with metformin. Galangin provides multidimensional protection against letrozole-induced ovarian dysfunction by alleviating oxidative stress, inflammation, and dysregulation of the PI3K/pAKT/PTEN pathway. These findings support the potential of galangin as a safe, multitarget natural adjunct for managing PCOS.

Empagliflozin as a potential therapy for PCOS: Restoring hormonal balance and ovarian function in a letrozole-induced rat model.

Integrative metabolomics and machine learning reveal the toxic mechanisms of elaidic acid in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic condition affecting reproductive health, marked by disrupted ovulation, excessive androgen levels, and impaired endometrial receptivity. Oxidative stress is an important part of its pathophysiological process. Atractylenolide III (ATIII), a major sesquiterpene lactone derived from Atractylodes macrocephala Koidz., exhibits antioxidant properties; however, its role and molecular mechanisms in PCOS have not yet been explored. A PCOS rat model was established using dehydroepiandrosterone (DHEA) and subsequently treated with ATIII or metformin. Estrous cycle, ovarian morphology, serum hormone levels, glucose metabolism, and endometrial receptivity markers were evaluated. Oxidative stress status was evaluated by detecting the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and antioxidant-related genes and proteins expression. Ovarian transcriptomic sequencing was performed to explore potential molecular pathways associated with ATIII treatment. ATIII administration was associated with restoration of estrous cycle, reduction of cystic follicles, improvement of ovulation, and normalization of serum hormones and metabolic parameters in PCOS rats. Ovarian stromal fibrosis was attenuated, and morphological and molecular markers of endometrial receptivity were improved. ATIII treatment was accompanied by increased SOD activity, decreased MDA accumulation, and restoration of NRF2-related antioxidant genes and proteins. Transcriptomic analysis revealed enrichment of oxidative stress-related pathways, within which Cybb (encoding NOX2) was found as a differentially regulated gene that was upregulated in PCOS ovaries then reduced following ATIII treatment. ATIII improves reproductive and metabolic abnormalities and enhances endometrial receptivity in a PCOS rat model. These results are mediated by attenuation of ovarian oxidative stress and modulation of Cybb-related redox signaling. These data offer mechanistic insight into the pharmacological potential of ATIII in PCOS.

Ursolic Acid (UA), a naturally occurring pentacyclic triterpene, was isolated from Ochrosia elliptica. Polycystic Ovary Syndrome (PCOS) a prevalent endocrine disorder characterized by hyperandrogenism, insulin resistance, and chronic inflammation. In this study, we investigate the role of UA in alleviating the symptoms of PCOS, focusing on its biochemical, hormonal, and histopathological effects in a rat model. Using adult female Wistar Albino rats, PCOS was induced through letrozole administration. The rats were then treated with UA at two different doses (25 and 50mg/kg), alongside a control group and a standard ovulation-inducing medication, clomiphene citrate (1mg/kg). Biochemical analyses showed that PCOS induction significantly increased serum malondialdehyde (MDA) levels by approximately 1.21-fold, while markedly reducing superoxide dismutase (SOD) and catalase (CAT) activities (p ≤ 0.05) by approximately 0.48-fold, relative to negative control. Treatment with UA (50mg/kg) dose-dependently restored oxidative balance, reducing MDA (~ 0.82-fold) and elevating SOD (~ 2.39-fold) and CAT (~ 2.11-fold) activities toward PCOS values (p ≤ 0.05). Hormonally, PCOS rats exhibited elevated luteinizing hormone (LH) and testosterone levels by approximately 1.70-fold, compared to the negative control (p ≤ 0.05). Both doses of UA significantly lowered LH and testosterone, with the 50mg/kg dose achieving reductions comparable to clomiphene citrate (p ≤ 0.05). Histopathological examination showed improved ovarian morphology with reduced cystic follicles and increased corpus lutea in UA-treated groups. Furthermore, UA downregulated key genes involved in steroidogenesis and oxidative stress response, suggesting a multifaceted mechanism of action. The findings highlight UA's potential as a novel therapeutic option for managing PCOS symptoms, emphasizing the need for further research into its efficacy and safety in clinical applications.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder characterized by hormonal imbalances, ovarian dysfunction, and metabolic irregularities. Jiawei Zaoqi Decoction (JWZQD), a Traditional Chinese Medicine (TCM) formulation, has shown potential as a multi-targeted therapeutic intervention for PCOS. However, its underlying mechanisms remain unclear. In this study, we explored the therapeutic effects and molecular mechanisms of JWZQD in managing PCOS. We employed a multi-model approach integrating clinical data, animal models, and mechanistic assays. Clinical efficacy was evaluated in a cohort of PCOS patients, while a letrozole- induced rat model combined with a high-fat diet was used to assess reproductive and metabolic outcomes. Network pharmacology, Gene Ontology, KEGG enrichment, and protein-protein interaction analyses were applied to identify key targets and pathways. Granulosa-cell experiments under oxidative stress and insulin stimulation were performed for functional validation. JWZQD administration significantly decreased serum luteinizing hormone and testosterone levels, improved insulin, and restored estrous cyclicity in PCOS patients and rats. Histology and ultrasound revealed reduced cystic follicles and normalized ovarian stroma. Bioinformatic analyses identified cellular senescence and AGE-RAGE signaling as core pathways, with quercetin and fisetin emerging as critical bioactive compounds. In vitro, quercetin and fisetin suppressed senescence markers (p21, p53, γH2AX) and rescued granulosa-cell proliferative capacity, confirming the network predictions. These findings provide mechanistic insight into how JWZQD ameliorates PCOS, highlighting its multi-targeted regulation of endocrine, metabolic, and ovarian functions. Importantly, our results suggest that targeting granulosa-cell senescence may represent a novel therapeutic strategy. JWZQD mitigates PCOS by modulating AGE-RAGE-mediated granulosa-cell senescence through its active compounds quercetin and fisetin. This study supports the clinical potential of JWZQD as an alternative or complementary therapy for PCOS.

BackgroundQi Gong Wan (QGW) is a herbal formula which is used for treating infertility associated with polycystic ovary syndrome (PCOS). However, the mechanism of action remains unclear. This study aimed to investigate whether QGW enhances endometrial receptivity in a PCOS with insulin resistance (PCOS-IR) rat model and to explore the underlying molecular mechanisms and primary active constituents.Materials and methodsA PCOS with insulin resistance (IR) rat model was established using dehydroepiandrosterone (DHEA) and a high-fat diet. Rats were treated with QGW or metformin as a positive control. Network pharmacology and molecular docking were used to identify potential drug-disease targets and active components. Endometrial receptivity was evaluated by assessing key markers—including HOXA10, HOXA11, ITGβ3, LIF, GLUT4, and IGFBP1—using histological examination, scanning electron microscopy (to observe pinopode formation), quantitative real-time PCR, Western blot, and immunohistochemistry. SiRNA-mediated knockdown of Hoxa11 was employed to validate its functional role. Network pharmacology and molecular docking techniques were applied to identify potential drug–disease targets and active constituents.ResultsQGW significantly restored regular estrous cycles, reduced testosterone, fasting insulin, and HOMA-IR levels, and improved ovarian morphology in PCOS-IR rats. Network pharmacological analysis identifies HOXA10, HOXA11, and IGFBP1 as core targets. Molecular docking studies demonstrate that wogonin exhibits strong binding affinity with these targets. QGW upregulates the expression of endometrial receptivity markers (HOXA10, HOXA11, ITGβ3, LIF, GLUT4, IGF1) while downregulating IGFBP1 and IL-6 levels. Additionally, Qigui Wenjing Formula promotes pinopode formation and normalizes estrogen/progesterone receptor expression. When Hoxa11 gene expression is suppressed, this formula can reverse the consequent decline in receptivity-related gene expression.ConclusionsQGW is capable of enhancing the expression of genes related to endometrial receptivity in PCOS model rats and increasing the number of pinopodes, thereby improving the endometrial receptivity in PCOS rats. The results suggest that QGW may improve endometrial receptivity potentially through upregulation of Hoxa11 accompanied by increased Itgβ3 and decreased Igfbp1. However, whether Hoxa11 directly binds to the promoter regions of relevant genes requires further validation. Network pharmacology and molecular docking suggest that wogonin may be an active constituent with considerable potential, though its specific contribution requires further validation through in vivo and in vitro functional experiments.

The present study aimed to evaluate the therapeutic potential of the Unani formulation Ark-e-Kasni in alleviating the symptoms of polycystic ovary syndrome (PCOS). In the present study, letrozole and a high-fat diet (HFD) were used to induce PCOS-like symptoms in rats. After induction, different groups were treated with varying doses of Ark-e-Kasni (5, 10, and 20 mL/kg), metformin, and finasteride. At the end of treatment, blood and ovaries were collected for biochemical and histological analysis. A significant weight gain and prolonged diestrous phase were observed in PCOS rats, accompanied by a considerable elevation in LH (42.52 ± 0.90 mIU/mL) and testosterone (8370 ± 122.18 pg/mL), and a low level of FSH (11.86 ± 0.43 mIU/mL). Moreover, an increase in insulin (14.31 ± 0.35 mIU/mL), TNF-α (358.81 ± 9.81 pg/mL), IL-1β (143.74 ± 3.39 pg/mL), and IL-6 (154.04 ± 2.04 pg/mL), and a reduction in SOD, CAT, and GSH were noticed. While the Ark-e-Kasni restored the levels of LH (30.97 ± 1.04 mIU/mL), testosterone (5651.83 ± 182.69 pg/mL), FSH (15.66 ± 0.56 mIU/mL), insulin (5.48 ± 0.23 mIU/mL), TNF-α (212.16 ± 8.66 pg/mL), IL-1β (78.79 ± 1.46 pg/mL), and IL-6 (74.53 ± 1.60 pg/mL), and lipid markers. Histological and microscopic analysis showed reduced cystic follicles and enhanced corpus luteum formation, improving ovarian morphology. The findings suggest that Ark-e-Kasni ameliorates PCOS through diverse molecular mechanisms. Ark-e-Kasni may modulate steroidogenic enzyme activity to reduce hyperandrogenism, enhance insulin sensitivity through the PI3K/Akt pathway, and inhibit the downstream inflammatory pathway of NF-κB.

Metformin improves polycystic ovary syndrome through the regulation of granulosa cell proliferation and apoptosis via the miR-103a-3p/PTEN signaling pathway.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by ovarian dysfunction and hyperandrogenism. This study aimed to evaluate the therapeutic potential of nicotinamide mononucleotide (NMN) in reducing PCOS-associated hyperandrogenism and to investigate the underlying inflammatory mechanisms. Female Sprague-Dawley rats were divided into three groups: control, PCOS model, and PCOS model treated with NMN. PCOS was induced via continuous letrozole administration combined with a high-fat diet for 30 days. Subsequently, the NMN-treated group received NMN supplementation for an additional 30 days. NMN administration significantly reduced body weight and serum testosterone levels in PCOS rats and restored regular estrous cyclicity. Transcriptomic analysis of ovarian tissue revealed significant activation of inflammatory and steroidogenic pathways. Further investigation demonstrated upregulated expression of pyroptosis-related molecules (NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18) in ovarian tissue from PCOS rats and in inflammatory cytokine-exposed granulosa cells. NMN treatment effectively suppressed these pyroptosis markers. Additionally, inflammation increased the expression of key androgen biosynthesis enzymes, including CYP11A1, CYP17A1, and 3β-HSD. NMN mitigates hyperandrogenism in PCOS, likely by inhibiting granulosa cell pyroptosis through suppression of the NLRP3 inflammasome pathway.

Polycystic ovary syndrome (PCOS) has been associated with conflicting effects on bone mass, underscoring the need for deeper investigation into its impact on skeletal health. This study aimed to assess the expression of osteoporosis-related genes in femoral bone, alongside hormonal profile (bone-related hormones) alterations, across aging in a rat model of PCOS compared to controls. Femoral bone RNA was extracted from rat model of PCOS and controls (n = 10-13 per group) at 3, 10, and 18months of age. The expression of IL-11, DKK1, RANKL, AKT1, IGF-1, EphB4, STAT3, and CTNNB1 genes was quantified via Real-Time PCR. Concurrently, serum levels of Anti-Mullerian Hormone (AMH), calcitonin, cortisol, total testosterone (TT), and vitamin D3 were measured using ELISA. A significantly elevated expression of IL-11, DKK1, RANKL, AKT1, and IGF-1 genes, accompanied by a decreased expression of EphB4 and STAT3 in the femoral bone of rat model of PCOS compared to controls, was observed. Additionally, rat model of PCOS exhibited higher serum levels of AMH, cortisol, and TT, whereas calcitonin and vitamin D3 levels were decreased. These molecular and hormonal alterations highlight a dysregulation in bone metabolism associated with PCOS and suggest that PCOS may represent a substantial risk factor for osteoporosis later in life. The employed rat model thus offers a valuable platform for elucidating the cellular and molecular mechanisms contributing to bone mass disorders in PCOS, facilitating the development of targeted therapeutic strategies.

This study investigated the therapeutic effects of Dapansutrile, a selective NLRP3 inflammasome inhibitor, on ovarian dysfunction in a dihydrotestosterone (DHT)-induced polycystic ovary syndrome (PCOS) rat model. Thirty adult female Wistar rats were allocated to control, PCOS + saline, and PCOS + Dapansutrile groups. PCOS was induced by subcutaneous DHT pellet implantation, followed by 28 days of intraperitoneal saline or Dapansutrile (100 mg/kg/day). Ovarian histology (follicle counts, fibrosis) and biochemical parameters (hormones, inflammatory and oxidative markers) were assessed. DHT exposure disrupted folliculogenesis, reducing primary (P < 0.001), secondary (P < 0.001), and tertiary follicles (P = 0.004), and markedly increased fibrosis (P < 0.001). Dapansutrile significantly enhanced primary (P < 0.01) secondary (P < 0.05) and tertiary follicle counts (P < 0.05), alleviated ovarian fibrosis (P < 0.001). Biochemically, PCOS rats exhibited elevated AMH, IGF-1, TNF-α, TLR4, MyD88, NF-κB, NLRP3, caspase-1, IL-1β, IL-18, and TGF-β1, alongside depleted ovarian GSH. Treatment with Dapansutrile attenuated inflammatory and fibrotic markers, elevated GSH, and decreased AMH and IGF-1, without altering insulin levels. Collectively, these findings provide the first evidence that Dapansutrile alleviates PCOS-induced ovarian dysfunction by suppressing inflammasome-driven inflammation, oxidative stress, and fibrosis, thereby improving follicular maturation and reducing stromal fibrosis in a hyperandrogenic PCOS model.