Journal of Ovarian Research最新文献

{"title":"Noninvasive markers for warning premature ovarian insufficiency: a Mendelian randomisation study.","authors":"Hangjing Tan, Jing Zhao, Baisheng Wang, Yanping Li","doi":"10.1186/s13048-025-01696-1","DOIUrl":"10.1186/s13048-025-01696-1","url":null,"abstract":"<p><strong>Background: </strong>Early diagnosis and early delivery are the main strategies for the treatment of premature ovarian insufficiency (POI). However, POI warning markers, especially those that can be detected through noninvasive methods, are very limited; therefore, the identification of noninvasive markers for POI is urgent.</p><p><strong>Methods: </strong>We acquired POI GWAS summary statistics from the FinnGen database. The metabolome, circulating plasma proteins, gut microbiota, immunophenotypes, circulating microRNAs (miRNAs), and two proteomes were obtained for two-sample Mendelian randomization (MR). Specifically, we employed inverse variance weighted (IVW) as the main method to calculate the MR effect estimates. eQTL data (from the eQTLGen Consortium) were employed for SMR. Hub genes were identified using the String database and Cytoscape software. Potential mechanisms of POI were identified via pathway enrichment analysis of the identified genes and miRNAs.</p><p><strong>Results: </strong>Three metabolites (sphinganine-1-phosphate levels, X-23636 levels, 4-methyl-2-oxopentanoate levels), two circulating plasma proteins (fibroblast growth factor 23 levels, neurotrophin-3 levels), one gut microbiota (faecalibacterium abundance), one immunophenotype (HVEM on naive CD8 + T cells), 23 miRNAs (miR-500a-3p, miR-555, miR-584-5p, miR-642a-5p, miR-671-3p, miR-1324, miR-6870-3p, miR-1468-5p, miR-146a-3p, miR-221-3p, miR-3121-5p, miR-3184-3p, miR-3185, miR-335-5p, miR-4302, miR-4506, miR-6808-5p, miR-6894-5p, miR-145-5p, miR-149-3p, miR-23a-3p, miR-3141, and miR-374b-5p), and three hub genes (ESR1, ERBB2, and GART) serve as warning markers for POI. Enrichment analysis indicated that pathways such as glutathione metabolism and the PI3 kinase pathway may be involved in mechanisms regulating POI.</p><p><strong>Conclusion: </strong>Our results are the first to identify noninvasive predictors for POI via MR, providing contributions for early warning and fertility guidance for clinical POI patients.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"127"},"PeriodicalIF":3.8,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266404","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":"Management paradigm for ovarian neuroendocrine carcinoma: a systematic review.","authors":"Kemala Isnainiasih Mantilidewi, Gatot Nyarumenteng Adhipurnawan Winarno, Ali Budi Harsono, Dodi Suardi, Yudi Mulyana Hidayat, Andi Kurniadi, Siti Salima, Febia Erfiandi, Aini Sofa Haniah, Nirmala Chandralega Kampan","doi":"10.1186/s13048-025-01701-7","DOIUrl":"10.1186/s13048-025-01701-7","url":null,"abstract":"<p><strong>Introduction: </strong>Neuroendocrine neoplasms (NENs) of the female genital tract are rare, comprising only 1-2% of gynecologic tumors, with ovarian neuroendocrine carcinoma (O-NEC) accounting for less than 1% of all ovarian cancers. Despite its rarity, O-NEC is a highly aggressive tumor with poor prognosis and significant diagnostic complexity, warranting focused clinical attention and demand greater awareness to improve diagnostic and therapeutic strategies.</p><p><strong>Methods: </strong>This systematic review analyzed management paradigm for O-NEC through a comprehensive search on the databases PubMed, Science Direct, Wiley, Springer Link, Google Scholar and Cochrane Central Register of Controlled Trials that was performed on August 1st, 2024.</p><p><strong>Results: </strong>A comprehensive search on August 1st, 2024, identified 21 eligible studies (6 retrospective cohorts, 12 case reports, 3 case series), encompassing 923 cases of O-NEC. The most common subtypes were small-cell (40%) and large-cell (39.8%) NEC. Most patients presented with advanced-stage (Stage III-IV: 52%). Immunohistochemical markers included synaptophysin (84%), chromogranin A (64.2%), CD56 (69%), and NSE (77.7%). Treatment varied from surgery alone (35%) or surgery plus chemotherapy (32%) being most common. No standardized regimen of chemotherapy was identified with etoposide/cisplatin and paclitaxel/carboplatin were most frequently used. Survival outcomes were poor, with median overall survival ranging from 11 to 23.5 months. The stage at diagnosis was a crucial prognostic factor.</p><p><strong>Conclusions: </strong>The O-NEC is a rare, heterogeneous malignancy with diverse histopathology, variable immunohistochemical profiles, and generally poor prognosis. Early-stage disease may be managed with surgery alone, while advanced stages require multimodal treatment including surgery with adjuvant platinum-based chemotherapy. Due to limited cases and predominantly retrospective data, standardized diagnostic and treatment protocols are lacking. Prospective multicenter studies and centralized registries are needed to improve understanding and patient outcomes.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"125"},"PeriodicalIF":3.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258302","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":"Silencing of STX4 inhibits the proliferation, migration and invasion of ovarian cancer cells via EMT/MMP2/ CCND1 signaling pathway.","authors":"Wenfeng Ye, Chunyan Xue, Linlin Chen, Xiangnan Chen, Dachuan Zhang","doi":"10.1186/s13048-025-01705-3","DOIUrl":"10.1186/s13048-025-01705-3","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer (OC) is one of the most common malignant tumors of the female reproductive system and 55-75% of patients relapse after surgery and standard postoperative chemotherapy and radiotherapy. Syntaxin4 (STX4) is localized in the plasma membrane and plays a role in the occurrence, development, invasion and metastasis of cancer cells.</p><p><strong>Objective: </strong>To investigate the changes in the biological behavior and effects of STX4 gene silencing on the invasion and metastasis of OC cell lines.</p><p><strong>Methods: </strong>The proliferation, migration and invasion abilities of two groups of OC cell lines SK-OV-3 and CAOV-3 constructed with an interfering plasmid (pLVX-shRNA1-STX4-shRNA) and a negative control plasmid (pLVX-shRNA1-nonspecific-shRNA), were examined via Cell Counting Kit-8, Transwell and scratch assays. The EMT markers vimentin and E-cadherin, MMPs (MMP1, MMP2 and MMP9) and CCND1 were used to explore the possible molecular mechanism of STX4 by which STX4 affects OC cells behavior, after which the effect of STX4 gene silencing on the proliferation of OC cells in vivo was tested.</p><p><strong>Results: </strong>After STX4 silencing, the biological behaviors of ovarian cancer cells including proliferation, migration and invasion, were significantly weakened. The results revealed that the E-cadherin, MMP2 and CCND1 levels of both OC cell lines were decreased after STX4 gene silencing. Animal models of STX4 gene silencing showed the tumorigenicity of tumor cells was reduced.</p><p><strong>Conclusion: </strong>We demonstrated for the first time that STX4, an important regulator of OC progression, was associated with the growth and metastasis of OC cells through correlations with EMT, MMP2, and CCND1, suggesting its potential as a new therapeutic target for OC.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"124"},"PeriodicalIF":3.8,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248369","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":"Accurate prediction of benign and malignant adnexal tumors in surgical resection and conservative treatment: construction and external validation of a diagnostic model based on CEUS, HE4, and O-RADS US v2022 evaluation.","authors":"Chun Liu, Yi Zhu, Keju Dai, Bo Tan, Hao Dong, Jing Lin, Rong He, Man Lu, Yuan Li","doi":"10.1186/s13048-025-01707-1","DOIUrl":"10.1186/s13048-025-01707-1","url":null,"abstract":"<p><strong>Purpose: </strong>To establish a diagnostic model combining contrast-enhanced ultrasound (CEUS), human epididymis protein 4 (HE4), and Ovarian-Adnexal Reporting and Data Systems (O-RADS) US v2022, verify its diagnostic efficacy, and compare it with subjective evaluation.</p><p><strong>Methods: </strong>From January 2018 to August 2021 (the test group) and from September 2021 to September 2022 (the validation group), the data of patients classified as O-RADS US v2022 categories 2 to 5 who underwent adnexal ultrasound examinations were prospectively and continuously collected. In the test group, univariate and multivariate analyses were used to explore the relationship between age, body mass index (BMI), maximum diameter of the lesion, menopausal status, HE4, cancer antigen 125 (CA125), and the characteristics of CEUS and malignant lesions. Selecting independent influencing factors to construct diagnostic model, which was validated in the external validation group and compared with subjective evaluation.</p><p><strong>Results: </strong>The test group included 563 patients (mean age, 48.7 ± 13.2), and the validation group included 246 patients (mean age, 47.6 ± 12.9). Univariate and multivariate analyses showed that enhancement time, enhancement intensity, dynamic changes, and HE4 were independent influencing factors for predicting adnexal malignant tumors. In the validation group, the sensitivities and specificities of O-RADS US v2022, O-RADS US v2022 + CEUS, O-RADS US v2022 + CEUS + HE4, and subjective assessment were 88.89% and 70.69%, 94.44% and 79.31%, 91.67% and 92.53%, and 93.09% and 89.66% respectively. In addition, the combined diagnostic performance of O-RADS US v2022, CEUS and HE4 (AUC = 0.980) was higher than that of O-RADS US v2022 alone (AUC = 0.876, P < 0.001) and the combination of O-RADS US v2022 + CEUS (AUC = 0.908, P < 0.001), and was comparable to the subjective evaluation (AUC = 0.963, P = 0.192).</p><p><strong>Conclusions: </strong>The combined diagnostic model of O-RADS US v2022, CEUS and HE4 can improve the specificity of adnexal ultrasound diagnosis without sacrificing sensitivity, and it has high reliability.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"123"},"PeriodicalIF":3.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248368","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":"Mast cell tryptase-PAR2 axis promotes ovarian fibrosis through RNF152-mediated stabilization of Bcl-xL.","authors":"Xiang Zhang, Jun Zhang, Chaojun Wang","doi":"10.1186/s13048-025-01704-4","DOIUrl":"10.1186/s13048-025-01704-4","url":null,"abstract":"<p><strong>Background: </strong>Our research aimed to study the effect and mechanism of tryptase on ovarian fibrosis.</p><p><strong>Methods: </strong>The POI mouse model was established by cisplatin at a dose of 1.5 mg/kg for ten days, while the control mice were given the same volume of saline. C57BL/6 female mice were intraperitoneally injected with 10 mg/kg cromolyn (n = 20 per group) or sterile saline (n = 20 per group) at two days before cisplatin treatment to assess the effect of cromolyn sodium on ovarian function and fibrosis. The ovaries of each mouse were collected for histological examination and collagen levels analysis. The effects of mast cells and tryptase on collagen I protein expression were investigated in primary mouse ovarian theca-stroma cells in vitro. The levels of sex hormones and tryptase were determined by ELISA.</p><p><strong>Results: </strong>Tryptase secreted by activated mast cells induced COL1A1 and COL1A2 production, two subunits of collagen I in mouse theca-stroma cells by protease-activated receptor-2 signaling. Inhibition of PAR2 or Bcl-xL attenuated the increases of COL1A1 and COL1A2 caused by tryptase. In addition, knockdown of RNF152 reversed the downregulation of collagen production caused by si-Bcl-xL. Clinically, tryptase levels in serum and follicular fluid were higher in both bPOI and POI patients than in controls. Tryptase concentrations in serum and follicular fluid were positively associated with follicle stimulating hormone (FSH) and negatively associated with anti-Müllerian hormone (AMH). Cromolyn sodium, a mast cell stabilizer, reduced collagen I production, but had no effect on hormone synthesis and follicle number in a cisplatin-induced POI mouse model.</p><p><strong>Conclusions: </strong>Tryptase might be associated with the pathogenesis of cisplatin-induced POI by promoting ovarian fibrosis through PAR2 via stabilization of Bcl-xL.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"122"},"PeriodicalIF":3.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234375","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":"Impact of obesity on proteomic profiles of follicular fluid-derived small extracellular vesicles: A comparison between PCOS and non-PCOS women.","authors":"Qiyuan Chang, Senlan Wang, Qingyun Mai, Canquan Zhou","doi":"10.1186/s13048-025-01703-5","DOIUrl":"10.1186/s13048-025-01703-5","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by ovulatory dysfunction, hyperandrogenism, and polycystic ovaries, significantly impacting reproductive health. Obesity, prevalent in 50-80% of PCOS patients, exacerbates metabolic disturbances and negatively influences assisted reproductive technology outcomes. This study investigates how obesity alters the proteomic profile of follicular fluid-derived small extracellular vesicles (FF-sEVs), aiming to elucidate mechanisms underlying reproductive impairments in this population.</p><p><strong>Methods: </strong>This study included women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), categorized into PCOS and non-PCOS control groups, further divided by BMI. Follicular fluid was collected, and sEVs isolated via ultracentrifugation. Proteomic analysis utilized data-independent acquisition (DIA) technology, with bioinformatics tools applied for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, along with protein-protein interaction (PPI) analysis. Statistical comparisons were performed using Analysis of variance (ANOVA) and t-tests to identify differentially expressed proteins. Correlation analysis assessed relationships between sEV protein profiles and reproductive outcomes, employing the Pearson correlation coefficient.</p><p><strong>Results: </strong>Proteomic profiling of sEVs revealed that the overweight/obese PCOS group had 180 upregulated and 256 downregulated proteins compared to lean counterparts. Additionally, differential functional analysis and PPI analysis indicated significant pathway and key proteins alterations in the PCOS group related to inflammation, while non-PCOS women demonstrated metabolic reprogramming and anti-inflammatory responses, suggesting a differential response to obesity that may preserve oocyte quality. Correlation analysis revealed significant associations between specific differentially expressed proteins and IVF/ICSI outcomes, while a protective role for Heat Shock Protein 90 Beta Family Member 1 (HSP90B1) protein was observed in the non-PCOS group. Lastly, validation through Western blot confirmed critical protein expression changes, particularly for S100 Calcium-binding Protein A8 (S100A8), emphasizing the impact of obesity on reproductive health outcomes in PCOS patients.</p><p><strong>Conclusions: </strong>In conclusion, our findings indicate that obesity exacerbates inflammation and oxidative stress in PCOS women, adversely affecting oocyte development and IVF/ICSI outcomes. In contrast, non-PCOS women exhibit protective metabolic and inflammatory adaptations. These insights underscore the necessity for tailored fertility management approaches, including weight loss strategies and specific interventions for PCOS patients, to optimize reproductive outcomes and enhance pregnancy success rates.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"121"},"PeriodicalIF":3.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225757","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":"Integrated multi-omics analysis identifies TLR4-mediated mechanisms in ATBC-induced ovarian dysfunction and female infertility: A network toxicology, transcriptomic, and Mendelian randomization study.","authors":"Jinfa Huang, Lingling Zeng, Qian Yang, Kaixian Deng","doi":"10.1186/s13048-025-01708-0","DOIUrl":"10.1186/s13048-025-01708-0","url":null,"abstract":"<p><strong>Background: </strong>Acetyl tributyl citrate (ATBC), a widely used plasticizer, has raised concerns regarding its reproductive toxicity. However, its molecular mechanisms in female infertility and ovarian damage remain poorly characterized. This study employs an integrative computational framework to elucidate ATBC-associated targets and pathways, with validation through genetic epidemiology and molecular docking.</p><p><strong>Results: </strong>We identified 137 ovarian damage-related and 143 infertility-related ATBC targets, refined to 19 and 30 hub genes respectively. Pathway analysis revealed significant enrichment in apoptosis, oxidative stress response, and PI3 K-AKT signaling (p < 0.05). Transcriptomic validation showed differential expression of 7/10 infertility-related and 9/10 ovarian damage-related hub genes. Mendelian randomization implicated TLR4 as protective against infertility (OR = 0.76, 95% CI:0.62-0.99; P = 0.049). Molecular docking confirmed strong binding affinities between ATBC and key targets (TLR4: Vina score = -4.8 kcal/mol; ESR1: -7.5 kcal/mol).</p><p><strong>Conclusions: </strong>This first multi-omics investigation of ATBC reproductive toxicity uncovers TLR4 as a critical mediator of ovarian dysfunction and infertility through inflammation-related pathways. Our findings provide novel mechanistic insights and suggest TLR4 modulation as a potential therapeutic strategy for chemical-induced reproductive disorders.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"120"},"PeriodicalIF":3.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216190","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 lncrna HMMR-AS1 promotes the malignant progression of ovarian cancer cells by regulating the miR-627-3p/PTN axis.","authors":"Jiaren He, Fei Tian, Jie Li, Yunxia Zhang, Zhaoping Chu","doi":"10.1186/s13048-025-01691-6","DOIUrl":"10.1186/s13048-025-01691-6","url":null,"abstract":"<p><strong>Background: </strong>LncRNAs are crucial regulators of ovarian cancer, playing a significant role in malignant transformation and closely linked to poor prognosis. Therefore, it is crucial to investigate the impact of lncRNAs on the malignant biological behavior of ovarian cancer and to understand their underlying molecular mechanisms.</p><p><strong>Methods: </strong>Gene expression levels were measured using qRT-PCR. The malignant biological behavior of cells was assessed through cell biological function assays. The binding sites of target genes were predicted through bioinformatics analysis, and gene targeting relationships were verified using a dual-luciferase reporter gene(DLRG) assay. Protein expression levels were analyzed using Western blotting.</p><p><strong>Results: </strong>In ovarian cancer cells, the expression levels of HMMR-AS1 and PTN were upregulated, whereas the expression of miR-627-3p was downregulated. Cell biological function experiments demonstrated that HMMR-AS1 and PTN could enhance the malignant behavior of ovarian cancer cells, while miR-627-3p exhibited the opposite effect. The DLRG assay indicated that lncRNA HMMR-AS1 directly targets miR-627-3p, with PTN identified as the target gene of miR-627-3p. Western blotting indicated that lncRNA HMMR-AS1 promoted the expression of PTN protein, while miR-627-3p inhibited it. Furthermore, it was demonstrated that miR-627-3p or PTN could partially reverse the effects of lncRNA HMMR-AS1 on the malignant phenotype of ovarian cancer cells.</p><p><strong>Conclusion: </strong>In summary, HMMR-AS1 is highly expressed in ovarian cancer and plays a carcinogenic role by regulating the miR-627-3p/PTN axis and suggest that targeting HMMR-AS1 is a potential strategy for ovarian cancer treatment.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"119"},"PeriodicalIF":3.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216191","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":"Plumbagin ameliorates ferroptosis of ovarian granulosa cells in polycystic ovary syndrome by down-regulating SLC7A5 m6A methylation modification through inhibition of YTHDF1.","authors":"ZhaoWei Cai, RuoPeng Zhang, RongJu Liu, Li Zhao, LiLing Zhou","doi":"10.1186/s13048-025-01700-8","DOIUrl":"10.1186/s13048-025-01700-8","url":null,"abstract":"<p><strong>Background and objective: </strong>Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disease in women of reproductive age. One of its core pathologies is ovarian granulosa cell (GC) dysfunction, and ferroptosis, as a novel cell death mode dependent on iron ions and lipid peroxidation, may be involved in the PCOS process, but the exact mechanism is unknown. Plumbagin (PLB) shows potential in PCOS treatment due to its antioxidant properties. The present study aimed to elucidate the molecular mechanisms by which PLB ameliorates mitochondrial dysfunction and ferroptosis in PCOS GCs through the YTH N6-methyladenosine RNA binding protein 1/L-type amino acid transporter 1 (YTHDF1/SLC7A5) axis.</p><p><strong>Methods: </strong>An in vitro model of PCOS was constructed by treating KGN cells with dihydrotestosterone (DHT), and PLB treatment, YTHDF1 knockdown (si-YTHDF1), and SLC7A5 overexpression (pcDNA 3.1-SLC7A5) were intervened respectively. Cell viability was measured by cell counting kit-8. Lactate dehydrogenase (LDH) release, adenosine triphosphate (ATP) level, iron ion, and lipid peroxidation (LPO) content were detected by commercial kits. Mitochondrial membrane potential (MMP) was analyzed by JC-1 staining combined with flow cytometry. Reactive oxygen species (ROS) levels were assessed by C11-BODIPY probe, oxidative stress indicators including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase were measured by kits, and Cytochrome C, Ferritin, mitochondrial transcription factor A (TFAM), glutathione peroxidase 4 (GPX4) and SLC7A5 expression were detected by Western blot. Fluorescence in situ hybridization, RNA immunoprecipitation, and m6A quantitative real-time polymerase chain reaction verified the interaction and translational regulation of YTHDF1 and SLC7A5.</p><p><strong>Results: </strong>DHT treatment significantly decreased KGN cell viability, MMP and ATP levels, increased LDH release, ROS, MDA, iron ions and LPO content, up-regulated Cytochrome C expression, and down-regulated Ferritin, TFAM, and GPX4 expression. Both PLB treatment and YTHDF1 knockdown significantly reversed the above changes, but YTHDF1 overexpression reversed the protective effect of PLB. YTHDF1 co-localized with SLC7A5 mRNA and enhanced its translation through m6A modification. YTHDF1 knockdown reduced SLC7A5 protein levels without affecting mRNA expression. SLC7A5 overexpression weakened the protective effect of YTHDF1 knockdown, resulting in decreased cell viability, deterioration of mitochondrial function, and increased ferroptosis.</p><p><strong>Conclusion: </strong>PLB ameliorates DHT-induced mitochondrial dysfunction and ferroptosis in KGN cells by inhibiting YTHDF1 expression, and its action is dependent on the mechanism by which YTHDF1 regulates SLC7A5 translation through m6A modification. Downregulating YTHDF1 or SLC7A5 significantly enhances GC survival and function.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"115"},"PeriodicalIF":3.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208789","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":"Mechanism study on the regulation of autophagy and oxidative stress through SIRT1/PI3K/AKT pathway by Liuwei Dihuang pill to improve ovarian function.","authors":"Jiawen Zhong, Guoxia Lan, Xiaoqing Ma, Wenyan Zhang, Bo Jiang, Ling Qin, Xiaorong Li, Yan Nian","doi":"10.1186/s13048-025-01689-0","DOIUrl":"10.1186/s13048-025-01689-0","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to examine the preventive impact of Liuwei Dihuang pill (LWDH) on ovarian injury and to elucidate its mechanism through in vivo and in vitro tests.</p><p><strong>Methods: </strong>Cyclophosphamide (CTX) was injected intraperitoneally and LWDH suspension was administered intragastrically to create a mouse model of primary ovarian insufficiency. Serum concentrations of hormones including AMH, E2 and FSH, alongside oxidative stress-related biomarkers such as SOD, GSH-Px and MDA, were measured using ELISA. By counting the autophagosomes in granulosa cells using electron microscopy and LC3 immunofluorescence labeling, the degree of autophagy was assessed. Finally, detect the expression levels of genes and proteins related to autophagy.</p><p><strong>Results: </strong>LWDH elevated the ovarian weight and improved the ovarian index in mice with ovarian injury. The LWDH-treated group exhibited considerably lower MDA levels and significantly higher SOD and GSH-Px levels than the CTX group. Meanwhile, the group treated with LWDH reduced the granulosa cells' excessive apoptosis. In addition, the LWDH-treated group exhibited reduced LC3 fluorescence intensity and fewer autophagosome counts in comparison to the CTX group. Similarly, the expression of LC3, an autophagy-related marker, was decreased and p62 was markedly elevated in comparison to the CTX group. These findings suggest that LWDH has a positive protective effect on ovarian injury mice by increasing antioxidant enzyme activity, improving ovarian tissue pathological damage, inhibiting granulosa cell apoptosis, and balancing granulosa cell autophagy. In addition, the expression levels of SIRT1 and PI3K/AKT signaling pathway related proteins in the LWDH treatment group were significantly higher than those in the CTX group, suggesting that LWDH may exert its protective effect by activating the SIRT1/PI3K/AKT signaling pathway.</p><p><strong>Conclusion: </strong>LWDH may suppress granulosa cell autophagy through the activation of the SIRT1/PI3K/AKT signaling pathway, hence enhancing ovarian function.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"118"},"PeriodicalIF":3.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208787","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}