Journal of Ovarian Research最新文献

{"title":"Comparative advantage and efficacy of natural products for polycystic ovary syndrome.","authors":"Jinsol Lee, Seonung An, Yeong Woo Kim, La Yoon Choi, Dae Yong Kim, Mi Hye Kim","doi":"10.1186/s13048-025-01756-6","DOIUrl":"10.1186/s13048-025-01756-6","url":null,"abstract":"<p><strong>Background: </strong>Natural products including Korean Medicine, Traditional Chinese Medicine and Campo medicine have been suggested to be suitable for polycystic ovary syndrome (PCOS), which is known to be a multifactorial disease, since current treatment for PCOS focuses on the amelioration of symptoms with adverse effects.</p><p><strong>Aim of the study: </strong>In this review, the ethnopharmacology and mechanisms of natural remedies including herbs, herbal formulation and acupunctures are introduced, providing a comprehensive insight for its advantage on PCOS.</p><p><strong>Materials and methods: </strong>We conducted a comprehensive literature search using PubMed, MEDLINE, and Google Scholar databases. Search terms included combinations of \"polycystic ovary syndrome,\" \"PCOS,\" \"natural product,\" \"herbal medicine,\" \"phytotherapy,\" \"acupuncture,\" and \"alternative and complementary medicine\".</p><p><strong>Results: </strong>A total of 2,514 articles were identified. After removing duplicates, we screened titles and abstracts for relevance. Studies were included if they involved: (1) preclinical in vivo or in vitro experiments using natural products in PCOS models; (2) randomized controlled trials (RCTs) or meta-analyses involving herbal, acupuncture, or combined treatments for PCOS; or (3) mechanistic evaluations. A total of 69 studies were selected for full-text analysis. Articles were excluded if they were non-original (e.g., reviews, commentaries), unrelated to PCOS, or did not include natural treatment modalities.</p><p><strong>Conclusion: </strong>The current status of the potential target pathway of natural products was assigned to three categories: research on the improvement of ovary and uterus quality, fertility and the weight loss for PCOS. However, there is no continuous study from basic research including in vitro and in vivo, and clinical trials. Large scale and more in-depth research are needed to verify their potential benefits for treating PCOS as a new drug.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"178"},"PeriodicalIF":4.2,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global profiling of protein lactylome in porcine granulosa cells.","authors":"Shuhao Fan, Ren Zhou, Haoyu Wen, Haibo Ye, Shuya Ma, Yu Bu, Peihuan Wang, Xianrui Zheng, Yueyun Ding, Zongjun Yin, Xiaodong Zhang","doi":"10.1186/s13048-025-01762-8","DOIUrl":"10.1186/s13048-025-01762-8","url":null,"abstract":"<p><strong>Background: </strong>In mammals, granulosa cells (GCs) use glycolysis as the main energy source for oocyte development. Lactate, the end product of glycolysis, covalently binds lysine. Residues in proteins through an enzymatic or non-enzymatic method known as lysine lactylation (Kla), which plays a role in epigenetics. Histone lactylation positively regulates reproduction. However, the roles of non-histone proteins in reproduction remain unclear. Based on the abundance of lactate in GCs, we first profiled the global lactylome in porcine GCs.</p><p><strong>Results: </strong>We identified 24,038 lactylation sites in 6,255 proteins, the largest number to date, indicating the richness of lactylation in GCs. Histones from porcine, humans, and mice are conserved at most sites, with some sites being specific to porcine such as H4K79. Kla proteins were significantly enriched in energy metabolism-related pathways, with all the enzymes involved in the tricarboxylic acid cycle and glycolysis undergoing lactylation. We also preliminarily illustrated the mechanism by which decreased protein lactylation induces ferroptosis.</p><p><strong>Conclusions: </strong>Our study provides a comprehensive understanding of lactylation in mammalian GCs and lays the foundation for subsequent studies on the lactylation-mediated regulation of female reproductive function.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"177"},"PeriodicalIF":4.2,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12333310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic role of the KRTAP5-AS1/miR-199b-5p/CYP19A1 axis in polycystic ovary syndrome pathogenesis.","authors":"Ping Tao, Xiaohong Yan, Zhanxiang Wang","doi":"10.1186/s13048-025-01746-8","DOIUrl":"10.1186/s13048-025-01746-8","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) pathogenesis involves dysregulated granulosa cell function, but molecular mechanisms remain unclear.</p><p><strong>Methods: </strong>High-throughput RNA sequencing was performed on ovarian granulosa cells from 6 PCOS patients and 3 controls to identify differentially expressed mRNAs. Bioinformatics analyses including ceRNA network construction predicted the KRTAP5-AS1/miR-199b-5p/CYP19A1 regulatory axis, which was experimentally validated through dual-luciferase reporter assays. qRT-PCR confirmed the expression patterns of these molecules in expanded clinical cohorts (38 PCOS vs. 30 controls), with Pearson correlation analysis examining relationships between gene expression and clinical parameters. Using the KGN granulosa cell line, functional studies included: (1) ELISA quantification of estradiol production; (2) proliferation assessment via CCK-8 and colony formation assays; and (3) apoptosis evaluation by flow cytometry and Bax/Bcl-2 protein analysis. These experiments were performed following both gain-of-function (overexpression) and loss-of-function (shRNA knockdown) manipulations of KRTAP5-AS1 and miR-199b-5p.</p><p><strong>Results: </strong>Through RNA sequencing of ovarian granulosa cells from 6 PCOS patients and 3 controls, we identified CYP19A1 as significantly upregulated in PCOS. Expanded validation in 38 PCOS vs. 30 controls confirmed elevated CYP19A1 and reduced miR-199b-5p in PCOS, with KRTAP5-AS1 showing negative correlation to miR-199b-5p and positive to CYP19A1. Clinically, CYP19A1 upregulation correlated with poor embryo quality, elevated testosterone, AMH, BMI, and infertility duration, while miR-199b-5p levels associated positively with embryo quality. In KGN granulosa cells, miR-199b-5p overexpression suppressed CYP19A1 expression and estradiol synthesis, whereas KRTAP5-AS1 overexpression alleviated this suppression via competitive miR-199b-5p binding. Functional studies demonstrated that miR-199b-5p overexpression combined with KRTAP5-AS1 knockdown inhibited proliferation, promoted apoptosis, and reduced estradiol production, while opposite manipulations reversed these effects.</p><p><strong>Conclusions: </strong>Our findings reveal that KRTAP5-AS1 modulates granulosa cell dysfunction in PCOS through the miR-199b-5p/CYP19A1 axis, highlighting miR-199b-5p as a potential therapeutic target for PCOS-related ovarian dysfunction and endocrine abnormalities.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"176"},"PeriodicalIF":4.2,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12333301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The efficacy and peripheral blood predictors in recurrent platinum-resistant ovarian cancer patients treated with immune checkpoint inhibitors.","authors":"Baoyue Pan, Xiaojing Zheng, Yongwen Huang, Wei Wei, Shije Xu, Siyu Chen, Jiaxin Yin, Yu Zhang, Jundong Li, Min Zheng","doi":"10.1186/s13048-025-01755-7","DOIUrl":"10.1186/s13048-025-01755-7","url":null,"abstract":"<p><strong>Introduction: </strong>The prognostic factors associated with recurrent platinum-resistant ovarian cancer treated with immune checkpoint inhibitor (ICI) therapy need to be identified.</p><p><strong>Methods: </strong>We retrospectively analyzed the efficacy of ICI therapy in patients with recurrent platinum-resistant ovarian cancer at our center. The number of CD8 + T cells and the expression of PD-L1 were assessed using immunohistochemical assays. A multi-analyte flow assay was used to detect the concentrations of 13 inflammatory cytokines. Both univariate and multivariate models were constructed using pretreatment clinical variables and cytokines.</p><p><strong>Results: </strong>We included 71 patients with recurrent platinum-resistant ovarian cancer treated with at least two cycles of anti-programmed cell death 1 (PD-1); the objective response rate was 36.62%, and the disease control rate was 78.87%. Elevated levels of interferon-alpha 2 (IFN-α2), IL-1β, and IL-12p70 in serum were associated with improved overall survival. Higher levels of monocyte chemoattractant protein 1 (MCP-1) correlated with longer overall survival and progression free survival. According to the results of the multivariate analysis, a high level of C-reactive protein (CRP) (> 10) independently predicted overall survival. Age, low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor-alpha (TNF-α), and MCP-1 were independently associated with progression-free survival. Chemotherapy containing platinum after immunotherapy progression achieved a partial response rate of 55.55%.</p><p><strong>Conclusion: </strong>The results of ICI combination therapy have demonstrated a response rate of over one third. Peripheral blood markers, such as cytokines, could potentially serve as predictors of immunotherapy efficacy in platinum-resistant ovarian cancer patients.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"175"},"PeriodicalIF":4.2,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of dietary fat on gut microbial composition and function in a mouse model of ovarian cancer.","authors":"Mariam M AlHilli, Naseer Sangwan, Alex Myers, Surabhi Tewari, Daniel J Lindner, Gail A M Cresci, Ofer Reizes","doi":"10.1186/s13048-025-01731-1","DOIUrl":"10.1186/s13048-025-01731-1","url":null,"abstract":"<p><strong>Objectives: </strong>The gut microbiome (GM) is pivotal in regulating inflammation, immune responses, and cancer progression. This study investigates the effects of a ketogenic diet (KD) and a high-fat/low-carbohydrate (HF/LC) diet on GM alterations and tumor growth in a syngeneic mouse model of high-grade serous ovarian cancer (EOC).</p><p><strong>Methods: </strong>Thirty female C57BL/6 J mice injected with KPCA cells were randomized into KD, HF/LC, and low-fat/high-carbohydrate (LF/HC) diet groups. Tumor growth was monitored with live, in vivo imaging. Stool samples were collected at the time of euthanasia and analyzed by 16SrRNA sequencing and shotgun metagenomic sequencing was performed to identify differential microbial taxonomic composition and metabolic function.</p><p><strong>Results: </strong>Our findings revealed that KD and HF/LC diets significantly accelerated EOC tumor growth compared to the LF/HC diet in a xenograft model. GM diversity was markedly reduced in KD and HF/LC-fed mice, correlating with increased tumor growth, whereas LF/HC-fed mice showed higher GM diversity. Metagenomic analyses identified distinct alterations in microbial taxa including Bacteroides, Lachnospiracae bacterium, Bacterium_D16_50, and Enterococcus faecalis predominantly abundant in HF/LC-fed mice, Dubsiella_newyorkensis predominantly abundant in LF/HC-fed, and KD fed mice showing a higher abundance of Akkermansia and Bacteroides. Functional pathways across diet groups indicated polyamine biosynthesis and fatty acid oxidation pathways were enriched in HF/LC-fed mice.</p><p><strong>Conclusions: </strong>These results highlight the intricate relationship between diet andthe gut microbiome in promoting EOC growth. The potential role of dietary interventions in cancer prevention and treatment warrants further investigation.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"174"},"PeriodicalIF":4.2,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12318416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring causal relationships between brain imaging-derived phenotypes and ovarian cancer risk: a bidirectional Mendelian randomization.","authors":"Ting Liu, Xiaoqian Tuo, Huifang Zhao, Yan Wang, Yu Jiang, Jiaojiao Lu","doi":"10.1186/s13048-025-01733-z","DOIUrl":"10.1186/s13048-025-01733-z","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer could induce alterations in both structure and function of the brain. This study employs Mendelian randomization (MR) to investigate the causal relationship between brain imaging-derived phenotypes (IDPs) and ovarian cancer, offering new insights into the potential clinical applications of IDPs for ovarian cancer risk assessment.</p><p><strong>Methods: </strong>This study identified 587 brain IDPs using structural and diffusion magnetic resonance imaging (MRI) data from the UK Biobank and data were sourced from two independent Genome-Wide Association Studies (GWAS). We selected single nucleotide polymorphisms (SNPs) as instrumental variables based on rigorous criteria. To evaluate the causal effects of IDPs on the risk of ovarian cancer, we employed five MR models: Inverse Variance Weighted (IVW), MR-Egger regression, Weighted median, Weighted mode, and Simple mode. Furthermore, we conducted a meta-analysis to provide additional validation for our results.</p><p><strong>Results: </strong>Forward MR analysis identified 72 IDPs that were significantly associated with the risk of ovarian cancer, with 65 remaining robust after conducting sensitivity tests. Conversely, reverse MR analysis indicated that 63 IDPs were influenced by ovarian cancer, highlighting a bidirectional causal relationship between these factors. The meta-analysis revealed that an increased cortical surface area of the right precentral gyrus was associated with a heightened risk of ovarian cancer, with an odds ratio (OR) of 1.139 (95% confidence interval [CI]: 1.037-1.250, P = 0.006, common effect model). In contrast, a larger volume of the right medial orbital frontal cortex was linked to a reduced risk of ovarian cancer, with an OR of 0.839 (95% CI: 0.744-0.946, P = 0.004, common effect model). Additionally, in the reverse MR analysis, a higher risk of ovarian cancer was associated with an increased fractional anisotropy (FA) in the right fornix and stria terminalis, while decreased orientation dispersion index (OD) in the left anterior corona radiata.</p><p><strong>Conclusions: </strong>This study provides compelling evidence of a causal relationship between IDPs and ovarian cancer risk. It suggests that IDPs might serve as valuable biomarkers for ovarian cancer risk assessment at brain-imaging levels and emphasize the need for further research to explore the biological mechanisms underlying these associations.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"173"},"PeriodicalIF":4.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12315427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of cell senescence and apoptosis in cyclophosphamide-induced premature ovarian failure in rats.","authors":"Jiaqi Wu, Yanmeng Wei, Qiangli Peng, Jing Zhu, Huacong Shi, Ting Zhao, Tao Yuan","doi":"10.1186/s13048-025-01759-3","DOIUrl":"10.1186/s13048-025-01759-3","url":null,"abstract":"<p><strong>Background: </strong>Premature ovarian failure (POF) is a clinical condition characterized by a diminished ovarian reserve occurring before the age of 40, significantly affecting female reproductive health. However, its exact pathogenesis remains unclear. This research aimed to examine the mechanisms of cyclophosphamide (CTX)-induced senescence and apoptosis in the ovarian and cerebral cortex tissues of rats to provide insights into delaying aging and protecting female reproductive health.</p><p><strong>Methods: </strong>A rat model of POF was established by intraperitoneal injection of CTX. Model efficacy was evaluated by measuring ovarian volume, weight, estrogen, and anti-Müllerian hormone levels. Serum marker changes were detected via enzyme-linked immunosorbent assay (ELISA). Senescence and apoptosis in cerebral cortical and ovarian tissues were observed using β-galactosidase (SA-β-gal) staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Western Blot and quantitative polymerase chain reaction (RT-qPCR) were employed to detect the expression levels of cell senescence- and apoptosis-related proteins and genes, verifying the correlation between POF and cellular senescence/apoptosis.</p><p><strong>Results: </strong>High-dose CTX induced POF. In rats with POF, the levels of anti-Müllerian hormone (AMH), estradiol (E2), and vitamin D (VD) significantly decreased (P < 0.0001), whereas the levels of testosterone (T) and insulin (INS) significantly increased (P < 0.0001). The number of senescent and apoptotic-positive cells in the ovarian and cerebral cortex tissues of rats with POF was substantially augmented (P < 0.05; P < 0.01). Additionally, the expression of senescence-related proteins cyclin-dependent kinase inhibitor 1 A (CDKN1A), cyclin-dependent kinase inhibitor 2 A (CDKN2A), tumor protein p53 (P53), apoptosis-related protein BCL2-Associated X Protein (Bax), and cysteine-aspartic acid protease 3 (caspase 3) was upregulated. In contrast, the expression of the anti-apoptotic protein BCL-2 was downregulated. The changes ranged from 1.7- to 7.1-fold. These findings demonstrated that high-dose CTX injection leads to cellular senescence and apoptosis, resulting in ovarian pathology.</p><p><strong>Conclusion: </strong>High-dose CTX induced POF in rats, resulting in aging and apoptosis in the cerebral cortex and ovarian tissues. Therefore, inhibiting cellular senescence and apoptosis may be a potential approach for restoring ovarian reserve function in POF.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"172"},"PeriodicalIF":4.2,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12315350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Premature ovarian insufficiency restoration after chemotherapy: current achievements and future prospects on its treatment or management.","authors":"Hamideh Aboutalebi, Shayan Vafaei, Mohammad Aboutalebi, Hengameh Dortaj, Fatemeh Alipour, Alireza Ebrahimzadeh- Bideskan","doi":"10.1186/s13048-025-01677-4","DOIUrl":"10.1186/s13048-025-01677-4","url":null,"abstract":"<p><p>One of the important discussions in assisted reproductive technology (ART) is to maintain fertility in those who are at risk of losing their fertility for various reasons, including cancer and the use of anti-cancer therapies, hence finding a way to maintain fertility during chemotherapy, is vital. Nowadays, in addition to successfully treating patients, oncologists have also focused their attention on preserving their patients' potential of the latter to conceive. Chemotherapy-related ovarian failure, which manifests as a non-physiological form of amenorrhea, can cause dysfunction of the ovary. It is hypothesized that chemotherapeutic agents may cause DNA damage, accelerate follicular apoptosis, oxidative stress, resulting in loss of ovarian reserve function. Hence investigation on utilization of alternatives in order to maintain ovarian function and fertility in cancer survivors seems important. This review provides an update on available and potential future prospects for fertility preservation in women treated with chemotherapy.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"171"},"PeriodicalIF":4.2,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12312501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperandrogenism-mediated YAP activation drives ovarian inflammation and pyroptosis in PCOS: implications for follicular dysfunction.","authors":"Tianyue Xu, Yu Xiang, Zichao Huang, Qi Zhu, Honghui Wu, Jieyu Cai, Linglin Weng, Hongshan Ge","doi":"10.1186/s13048-025-01757-5","DOIUrl":"10.1186/s13048-025-01757-5","url":null,"abstract":"<p><strong>Background: </strong>Hyperandrogenism and persistent chronic inflammation significantly contribute to ovarian dysfunction in polycystic ovary syndrome (PCOS). Although the exact connection between hyperandrogenism and inflammation in PCOS remains unclear, the Hippo pathway, also seems to be involved in the inflammatory response through YAP.</p><p><strong>Method: </strong>An in-vivo PCOS model of mice was constructed with dehydroepiandrosterone (DHEA) and YAP inhibitor Verteporfin (VP). YAP, inflammation and pyroptosis levels of ovarian tissues were detected in mice models. An in-vitro PCOS model of KGN cells was constructed with testosterone, and YAP was knocked down by lentivirus.</p><p><strong>Results: </strong>Increased levels of YAP in the ovarian tissues of the DHEA-treated mice were observed, alongside elevations in inflammation and pyroptosis levels, whereas Verteporfin reversed these alterations. The findings in KGN cells demonstrated that testosterone treatment results in elevation of YAP, inflammation and pyroptosis levels in granulosa cells. However, knocking down YAP in KGN cells curtailed testosterone-induced inflammation and pyroptosis.</p><p><strong>Conclusions: </strong>Hyperandrogenism in PCOS promotes ovarian inflammation by upregulating nuclear YAP, disrupting the inflammatory microenvironment, leading to abnormal ovarian pyroptosis, and ultimately impairing follicular function.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"170"},"PeriodicalIF":4.2,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12312577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Notch2 improves granulosa cell functions in premature ovarian failure by activating the Wnt2/β-catenin pathway.","authors":"Xia Liang, Nina Li, Senyan Wu","doi":"10.1186/s13048-025-01745-9","DOIUrl":"10.1186/s13048-025-01745-9","url":null,"abstract":"<p><strong>Background: </strong>Notch2 and Wnt2/β-catenin pathway improve granulosa cell (GC) functions, and there are interactions between Notch and Wnt/β-catenin in some cells. We aimed to investigate whether Notch2 improves GC functions in premature ovarian failure (POF) by activating the Wnt2/β-catenin pathway.</p><p><strong>Methods: </strong>Notch2 expression was interfered in mice or KGN cells, then, mice were treated with cyclophosphamide and busulfan intraperitoneally, and KGN cells were exposed to cyclophosphamide to establish POF models. In vivo, the number of follicles at different stages was counted, and interactions between Notch2 and Wnt2 were detected. In vitro, cell viability and cycle were measured. Additionally, hormone levels, oxidative stress (OS) degrees, cell apoptosis, Notch2 and Wnt2/β-catenin pathway-related genes were detected in vivo and in vitro. Finally, Wnt/β-catenin pathway inhibitor (IWR-1), agonist (SKL2001) and β-catenin knockdown were used.</p><p><strong>Results: </strong>Notch2 overexpression not only improved hormone levels, follicular development, OS degree and ovarian cell apoptosis, but also activated Wnt2/β-catenin pathway for POF mice. Moreover, Notch2 interacted with Wnt2 in POF mice. In vitro, Notch2 knockdown decreased cell viability, disrupted cell cycle, increased cell apoptosis, worsened hormone levels, promoted OS degree and inhibited Wnt2/β-catenin pathway for POF. Importantly, the protective effects of Notch2 overexpression and the worsening impacts of Notch2 knockdown on POF were reversed by IWR-1 and SKL2001. β-Catenin knockdown further impaired GC functions in POF models that underwent Notch2 and β-catenin knockdown.</p><p><strong>Conclusion: </strong>Notch2 may improve GC functions in POF by activating the Wnt2/β-catenin pathway, suggesting that the Notch2-mediated Wnt2/β-catenin pathway is a novel therapeutic target for POF.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"169"},"PeriodicalIF":4.2,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}