Journal of Ovarian Research最新文献

{"title":"Fatty acid metabolism of granulose cells and follicular fluid and their associations with embryo quality in normal-weight women with PCOS.","authors":"Ye Tian, Aiyuan Wang, Fang Li, Siyu Wang, Jie Shang, Kai Zhang, Xiaohong Bai","doi":"10.1186/s13048-025-01711-5","DOIUrl":"10.1186/s13048-025-01711-5","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is the most common reproductive-endocrine disorder in women of reproductive age. The granulosa cell metabolism correlated with oocyte competence. However, the alteration of fatty acid in granulosa cell of PCOS patients is unclear. Besides, obesity per se is related to dysfunction of oocyte quality. Hence, this study was aimed to comprehensively investigate the fatty acid alteration of oocyte environment and their associations with embryo quality in normal weight women with PCOS.</p><p><strong>Method: </strong>Two independent prospective cohorts included women with PCOS and age-BMI-matched controls that underwent IVF treatment were recruited. DIA-mass spectrometry-based proteomics analysis and absolute quantification of fatty acids were conducted in granulosa cells and follicular fluid from women with PCOS and controls, and then the relationship between fatty acid level and embryo quality in PCOS patients was analysed.</p><p><strong>Results: </strong>Proteomic analysis in cohort 1 revealed 205 differentially expressed proteins in the granulosa cells of normal-weight PCOS patients compared with those of controls. Functional enrichment analysis and metabolism score calculation revealed that fatty acid metabolism pathways, especially the biosynthesis of unsaturated fatty acids, were downregulated. The hallmark fatty acid metabolism score was negatively correlated with the total testosterone level and the AMH level (R=-0.52, P = 0.004; R=-0.64, P = 0.00017, respectively).Compared with those in the control group, the levels of the SFAs myristic acid (C14:0) and MUFAs nervonic acid (C24:1) in the follicular fluid of PCOS patients in cohort 1 were greater, whereas the ratio of PUFAs LA: ALA was lower, which were validated by cohort 2. C14:0 was moderately positively correlated with the basal LH level and LH/FSH ratio, even after correction for multiple comparisons. Receiver operating characteristic (ROC) analysis combining the C24:1, C14:0, and LA: ALA ratios with the seven fatty acid metabolic-related proteins revealed that the predictive accuracy for PCOS was 0.86.</p><p><strong>Conclusion: </strong>In normal-weight women with PCOS, fatty acid disturbance occurs in granulosa cells and follicular fluid, and also suggesting a role for C14:0, C24:1 and LA: ALA in PCOS patients, independent of obesity.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"130"},"PeriodicalIF":3.8,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293949","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":"Hyptolide induces ER stress-mediated cell death and enhances GSK3β-regulated cisplatin chemosensitivity in ovarian cancer.","authors":"Yusi Luluk Rahmania, Person Pesona Renta, Damar Nurwahyu Bima, Yu-Shan Lin, Ngoc Thang Nguyen, Pin-Yu Wang, Meiny Suzery, Wen-Tai Chiu","doi":"10.1186/s13048-025-01712-4","DOIUrl":"10.1186/s13048-025-01712-4","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer is a highly prevalent cancer among women with a high risk for relapse and drug resistance. Seventy eight percent of women diagnosed with ovarian cancer live for at least one year after diagnosis. Hyptolide, a natural compound, has been shown to act as an anti-inflammatory and antibacterial agent, and latest research shows that it acts as an anticancer agent. These properties indicate that hyptolide may be a potential treatment option for ovarian cancer, including chemoresistant cases; however, its effects in chemoresistant ovarian cancer have not yet been demonstrated, and the mechanisms underlying its induction of cell death remain unclear.</p><p><strong>Results: </strong>We found that hyptolide inhibited cell viability in ovarian cancer cell lines, regardless of their chemoresistance, and these effects were mediated by ER stress and the activation of GRP78 and ATF6. Combined treatment of cisplatin-resistant cell lines with hyptolide and cisplatin demonstrated a synergistic effect, enhancing apoptosis. Additionally, the reversal of chemoresistance with hyptolide treatment was mediated by β-catenin cytoplasm translocation leading to E-cadherin expression, ultimately promoting mesenchymal-epithelial transition.</p><p><strong>Conclusion: </strong>Our findings suggest that hyptolide induces ER stress-mediated cell death and overcomes cisplatin chemoresistance in ovarian cancer cells, supporting its potential use as a chemotherapeutic agent.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"129"},"PeriodicalIF":3.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284970","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":"Cryopreservation and transplantation of ovarian tissue as post-cancer tissue therapy and an activator of oogenesis.","authors":"Volodimir Isachenko, Bernd Morgenstern, Plamen Todorov, Evgenia Isachenko, Frank Nawroth, Maria Quassdorff, Mahmoud Salama, Nina Mallmann-Gottschalk, Markus Merzenich, Christine Skala, Gohar Rahimi","doi":"10.1186/s13048-025-01680-9","DOIUrl":"10.1186/s13048-025-01680-9","url":null,"abstract":"<p><p>In a recent publication (Reprod. Biomed. Online, 2024) it was presented point of view that, for post-cancer patients, in vitro fertilization (IVF) is a more effective method than ovarian tissue cryopreservation (OTC). In their commentary, Andersen et al. (Reprod. Biomed. Online, 2024) present nine distinct arguments advocating for the use of OTC. We fully agree with all these points. In support of the clinical application of the OTC procedure, we introduce two additional arguments. First, the transplantation of cryopreserved ovarian tissue can be considered as a form of tissue therapy. Moreover, OTC inherently serves as an activator of oogenesis. Second, during tissue dissection prior to OTC, a significant number of germinal vesicle (GV) oocytes can be retrieved, matured to the metaphase II (MII) stage, cryopreserved, and later used in IVF procedures.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"128"},"PeriodicalIF":3.8,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266402","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":"MACS and acellular autologous non-ovarian tissue scaffolds: a promising strategy for safe and efficient follicle transplantation in hematologic cancer.","authors":"Lijun Yin, Yating Zhao, Peiwen Zhang, Tongyun Qi, Peilin Han, Luya Cai, Jun Pan, Yongyi Yang, Jie Shi, Shi Feng, Yinying Zou, Kangxin He, Guoliang Xie, Weihua He, Xinhui Zhou, Jianhua Qian","doi":"10.1186/s13048-025-01687-2","DOIUrl":"10.1186/s13048-025-01687-2","url":null,"abstract":"<p><strong>Background: </strong>Advances in ovarian tissue cryopreservation offer new hope for young hematologic cancer patients. However, the risk of cancer cell reintroduction during transplantation remains a major concern, necessitating both effective tumor cell removal strategies and biocompatible scaffold development.</p><p><strong>Methods: </strong>We characterized decellularized adipose, peritoneal, and ovarian tissue scaffolds through H&E staining, immunofluorescence, SEM, and proliferation assays. Magnetic-activated cell sorting (MACS) efficiency was evaluated for reducing hematologic malignancy contamination. Follicle function was assessed via immunofluorescence and ELISA, while RNA-seq and qPCR compared gene expression across scaffolds.</p><p><strong>Results: </strong>Sodium dodecyl sulfate (SDS) decellularization effectively preserved extracellular matrix architecture across all tissues. In lipopolysaccharide (LPS)-induced leukocytosis models, MACS significantly reduced leukocyte contamination (p < 0.0001). Comparable follicle growth and hormone production (estrogen/progesterone/inhibin) were observed across scaffolds. RNA-seq analysis identified subtle differential expression in a small subset of follicle function-related genes, while the majority of genes exhibited conserved expression patterns across scaffolds.</p><p><strong>Conclusion: </strong>The results demonstrate that MACS effectively prevents tumor cell transmission during follicle transplantation. All decellularized scaffolds exhibited high follicular biocompatibility in this animal model, with non-ovarian scaffolds emerging as promising autologous alternatives for artificial ovary engineering.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"126"},"PeriodicalIF":3.8,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266403","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":"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}