Journal of Ovarian Research最新文献

{"title":"Non-syndromic premature ovarian insufficiency associated with monoallelic LIG4 mutation via haploinsufficiency.","authors":"Sha Yu, Xingyu Zhou, Yunhui Lai, Shuyan Tang, Shiling Chen","doi":"10.1186/s13048-026-02163-1","DOIUrl":"10.1186/s13048-026-02163-1","url":null,"abstract":"<p><strong>Background: </strong>Premature ovarian insufficiency (POI) is a heterogeneous reproductive disorder, with genetic factors, particularly defects in DNA damage response pathways, increasingly implicated in its pathogenesis. DNA ligase IV (LIG4) is a key enzyme in the non-homologous end joining (NHEJ) pathway responsible for repairing DNA double-strand breaks (DSBs). However, its role in non-syndromic POI remains unclear. This study aimed to investigate the potential contribution of LIG4 variants to non-syndromic POI.</p><p><strong>Results: </strong>Whole-exome sequencing identified a heterozygous frameshift variant in LIG4 (c.1271_1275del) in a three-generation Han Chinese family with non-syndromic POI, which co-segregated with affected individuals. AlphaFold-based structural modeling predicted truncation of the C-terminal XRCC4 interaction region. Functional experiments demonstrated that the mutant LIG4 protein showed reduced stability and was predominantly mislocalized to the cytoplasm of cells. In ovarian KGN cells, LIG4 depletion reduced cell viability, induced stress-associated cellular senescence, and impaired DNA damage repair capacity. In LIG4 knockout 293T cells, co-transfection of wild-type and mutant constructs revealed dose-dependent functional impairment, resulting in increased apoptosis under basal conditions and after phleomycin induced DNA damage, together with delayed repair of DSBs. Reanalysis of public single-cell RNA sequencing data further showed stage specific upregulation of LIG4 during oocyte maturation. Co-expression network analysis revealed enrichment in the Fanconi anemia pathway, phosphatidylinositol 3-kinase signaling pathway, and glycan metabolism.</p><p><strong>Conclusions: </strong>Our findings suggest that monoallelic LIG4 mutations may represent a potential genetic etiology for non-syndromic POI with sex-limited penetrance. While further validation in more physiologically relevant models is warranted, our data indicate that LIG4 haploinsufficiency may impair DSB repair and disrupt molecular pathways crucial for oocyte maturation and survival, highlighting a potential role of the NHEJ pathway in maintaining human ovarian function.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13556010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148317467","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":"Alpelisib enhances cisplatin mediated cytotoxicity in non-mutated, PIK3CA-dependent high-grade serous ovarian cancer.","authors":"Megha Mehrotra, Sourav Chakraborty, Elveera Saldanha, Diksha Joshi, Ajit Dhadve, Asmita Sakpal, Pratik Chandrani, Amita Maheshwari, Santosh Menon, Jaya Ghosh, Sudeep Gupta, Pritha Ray","doi":"10.1186/s13048-026-02171-1","DOIUrl":"10.1186/s13048-026-02171-1","url":null,"abstract":"<p><strong>Background: </strong>High-Grade Serous Ovarian Cancer (HGSOC) has a dismal five-year survival rate (< 30%) owing to late detection and recurrence caused by platinum resistance. Targeted therapy exhibits efficacy only within a limited patient population, warranting the need to identify new therapeutic regimes. Herein, we investigated the efficacy of a PIK3CA inhibitor, alpelisib, combined with cisplatin using malignant ascites-derived tumour cells from HGSOC patients, cell lines, patient derived xenografts.</p><p><strong>Methods: </strong>Malignant ascites-derived tumour cells were collected from treatment-naïve and relapsed HGSOC patients. The efficacy of the cisplatin-alpelisib combination in primary cells and p53 mutant cell lines was assessed through cell viability assays. Targeted next-generation sequencing was performed to identify somatic and germline mutations. Real-time PCR, clonogenic assay, chromatin immunoprecipitation, immunoblotting, immunofluorescence, pre-clinical tumour models, and patient-derived xenograft were used to identify and validate molecular determinants of treatment response.</p><p><strong>Results: </strong>The cisplatin-alpelisib combination induced significant apoptosis in 33% of patient samples and 80% of the responders had harbored amplification in PIK3CA gene. Intriguingly, primary tumor cells expressing p53 mutations-R196Q or R175H, in a PIK3CA non-mutated background conferred sensitivity to cisplatin-alpelisib. Expression of certain p53 mutants (R196Q, R175H, and R282W) in p53-null SKOV3 cells or EOC cells indigenously harboring p53-R175H (TOV112D) showed enhanced PIK3CA expression following cisplatin treatment. This effect was found to be associated with reduced occupancy of mutant p53, coupled with increased NFκB binding on the PIK3CA promoter, leading to enhanced PIK3CA transcription and susceptibility to the cisplatin-alpelisib combination. The combinatorial treatment effectively arrested TOV112D tumour growth (p53-R175H) but not A2780 (Wtp53) compared to cisplatin alone, and significantly reduced the ascites burden in a PDX mouse model. High somatic BRCA2 mutations were also observed without any association with the cisplatin-alpelisib efficacy in our cohort.</p><p><strong>Conclusion: </strong>Our findings highlight the potential of cisplatin-alpelisib treatment in a subset of HGSOC patients with PIK3CA overexpression, mediated either through gene amplification or transcriptional modulation, reflecting the wider application of alpelisib in PIK3CA-non-mutated ovarian cancer.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148302023","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":"Single-cell RNA sequencing in ovarian cancer: decoding the tumor microenvironment for personalized therapy.","authors":"Usamah Sayed, Shaker Al-Hasnaawei, Hayjaa Mohaisen-Mousa, Renuka Jyothi-S, Priya Priyadarshini-Nayak, Bethanney Janney-J, Gurjant Singh, Ashish Singh-Chauhan, Manoj Kumar-Mishra","doi":"10.1186/s13048-026-02132-8","DOIUrl":"10.1186/s13048-026-02132-8","url":null,"abstract":"<p><p>Ovarian cancer (OC) remains a leading cause of mortality among gynecological malignancies, largely due to profound inter- and intra-tumoral heterogeneity and the critical influence of the tumor microenvironment (TME). Comprising immune, stromal, endothelial, and extracellular matrix components, the TME orchestrates tumor progression, metastasis, and therapeutic resistance. Single-cell RNA sequencing (scRNA-seq) has revolutionized the study of OC by providing high-resolution insights into rare cellular subpopulations, dynamic transcriptional programs, and intercellular communication networks. These advances have facilitated the discovery of prognostic biomarkers, immune signatures, and novel therapeutic targets. Moreover, integration of scRNA-seq with spatial transcriptomics, multi-omics platforms, and artificial intelligence has expanded its potential to capture cellular complexity and refine patient stratification. Despite current challenges, including underrepresentation of specific cell types, technical variability, and high cost, scRNA-seq continues to drive progress in precision oncology. This review highlights recent applications of single-cell technologies in ovarian cancer, underscores their role in decoding TME biology, and explores future directions toward clinical translation and personalized therapeutic strategies.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148302068","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":"Association of hormone receptor-based pathological features with prognosis in high-grade serous ovarian carcinoma: a retrospective cohort study and nomogram construction.","authors":"Chengcheng Zhu, Hengliang Sun, Yonghong Luo, Dandan Ge, Shun Yao, Yi Wang, Meng Yan, Yuanyuan Lyu, Jiangli Liu","doi":"10.1186/s13048-026-02172-0","DOIUrl":"10.1186/s13048-026-02172-0","url":null,"abstract":"<p><strong>Background: </strong>High-grade serous ovarian cancer (HGSC) causes high mortality rates worldwide due to its insidious onset and poor prognosis. The statuses of hormone receptors (ER/PR) have been shown to have significant prognostic value in hormone-related tumors such as breast cancer, but their roles in HGSC remain unclear.</p><p><strong>Methods: </strong>This study retrospectively analyzed the relationship between estrogen receptor (ER) and progesterone receptor (PR) expression status, clinical features, and survival outcomes in 176 patients with HGSC. Kaplan-Meier analysis and univariate and multivariate Cox regression were used to identify prognostic factors. Propensity score matching (PSM) was applied to control for confounding, and a nomogram incorporating ER/PR status and other independent prognostic factors was developed. Internal validation was performed using repeated stratified 5-fold cross-validation and 1,000-bootstrap resampling.</p><p><strong>Results: </strong>ER/PR expression status was significantly associated with survival. The ER(+)/PR(+) group had the best prognosis, whereas the double-negative group had the worst. Combined ER/PR expression remained an independent prognostic factor in multivariate analysis (HR = 11.610, 95% CI: 6.225-21.653). The nomogram showed good predictive performance for 1-, 3-, and 5-year OS, with favorable discrimination and calibration in internal validation.</p><p><strong>Conclusion: </strong>Combined ER/PR expression status is an independent prognostic factor in HGSC. A nomogram integrating ER/PR status with clinicopathological variables may provide a practical tool for individualized risk assessment.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13536717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283781","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":"Novel approaches to modulate CAR-T cell function by targeting the tumor microenvironment in ovarian cancer.","authors":"Saber SamadiAfshar, Hossein Azizi, Meghdad Yeganeh, Sahel SamadiAfshar, Thomas Skutella","doi":"10.1186/s13048-026-02149-z","DOIUrl":"10.1186/s13048-026-02149-z","url":null,"abstract":"<p><p>Ovarian cancer (OC) remains one of the most lethal gynecological malignancies despite advances in conventional therapeutic approaches. The dismal approximately 30% five-year survival rate for advanced disease highlight the urgent need for innovative treatment strategies. Chimeric antigen receptor T (CAR-T) cell therapy, having revolutionized treatment paradigms in hematological malignancies, faces significant challenges when applied to the complex immunosuppressive tumor microenvironment (TME) of ovarian cancer. This comprehensive review investigates critical research questions regarding the extent to which cellular and molecular components of the ovarian cancer TME inhibit CAR-T cell cytotoxic function, and the signaling patterns associated with reduced CAR-T cell infiltration or persistence in tumor masses. We systematically examine the multifaceted immunosuppressive mechanisms within the ovarian cancer TME and evaluate breakthrough strategies designed to overcome these barriers, including next-generation CAR engineering, combinatorial therapeutic approaches, and innovative TME-modulating technologies. The insights presented here provide a crucial roadmap for translating CAR-T therapy from promising concept to clinical reality in ovarian cancer treatment, potentially transforming outcomes for patients with this recalcitrant malignancy where innovative therapeutic options are urgently needed.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283735","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":"Multiple Clustering Algorithms for Ovarian Cancer Subtyping (MCAOCS): identifying clinical phenotypes and treatment response in critical care.","authors":"Yamin Qiu, Zhengwen Qin, Huixian Zheng, Tao Wang, Runhong Liu, Jing Yang","doi":"10.1186/s13048-026-02167-x","DOIUrl":"10.1186/s13048-026-02167-x","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer (OC) patients admitted to the Intensive Care Unit (ICU) represent a critically ill population with significant heterogeneity, posing challenges for prognosis and personalized management. A robust subtyping system integrating multidimensional clinical data is urgently needed.</p><p><strong>Objectives: </strong>This study aimed to identify and characterize distinct clinical phenotypes of OC in critical care settings and investigate their associations with outcomes and subtype-specific treatment responses.</p><p><strong>Methods: </strong>This retrospective cohort study analyzed data from 448 ICU patients with OC across two critical care databases (MIMIC-IV and eICU). We employed a Multiple Clustering Algorithms for OC Subtyping (MCAOCS) approach to identify phenotypes. The robustness of subtypes was assessed through internal and external application. Survival analysis and Inverse Probability of Treatment Weighting (IPTW) were used to evaluate mortality and treatment-exposure association.</p><p><strong>Results: </strong>We identified two distinct clinical phenotypes from the MIMIC-IV discovery cohort (n = 259): Critical OC (n = 118) characterized by hemodynamic instability and high disease severity, and Stable OC (n = 141) with preserved organ function. The robustness and reproducibility of these phenotypes were assessed in the external eICU application cohort (n = 189). The Critical OC subtype demonstrated significantly higher mortality from 28 days to one year. Exploratory treatment-exposure analyses suggested subtype-specific associations: several ICU support and medication exposures were associated with lower 28-day mortality in the Critical OC subtype, whereas in the Stable OC subtype, only insulin and phenylephrine exposures retained statistical significance after multiple-testing correction. These findings should be interpreted as hypothesis-generating rather than causal.</p><p><strong>Conclusions: </strong>The MCAOCS-based binary phenotype system is robust and may have potential clinical utility, effectively stratifying ICU OC patients by mortality risk and suggesting subtype-specific treatment associations, thereby potentially facilitating precision critical care.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13523494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271535","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 mitochondrial dysfunction in premature ovarian insufficiency.","authors":"Chenyu Jia, Huihui Li, Ruotong Ju, Puhua Zhang, Li Peng, Tingting Xue, Xinyu Zhu, Shu Wang, Jiali Luo, Ruixiang Zhu, Xuan Jing, Xiangrong Cui","doi":"10.1186/s13048-026-02170-2","DOIUrl":"10.1186/s13048-026-02170-2","url":null,"abstract":"<p><p>Premature ovarian insufficiency (POI) is a clinical syndrome characterized by the decline of ovarian function in women under the age of 40, and its core pathological feature is the irreversible depletion of the ovarian reserve. Mitochondria serve as the central hub for energy metabolism and signal integration in ovarian cells, and their dysfunction drives POI progression through multiple cell death pathways and signaling cascades. This review systematically examines the multidimensional mechanisms by which mitochondrial damage leads to follicle depletion and proposes, for the first time, an integrated regulatory model termed \"mitochondrial damage - follicle fate decision.\" The review further identifies contradictory evidence, model limitations, and gaps in clinical translation within current research. Regarding therapeutic strategies, we evaluate the current status, safety risks, and ethical barriers of mitochondrial nutrients, stem cell therapy, gene editing, and mitochondrial replacement therapy. Finally, we propose a future research framework centered on mitochondrial dynamics and quality control, emphasizing the need for multi-omics integration and personalized interventions.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13520522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271483","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":"Low muscle mass predicts poor response to neoadjuvant chemotherapy in advanced ovarian cancer.","authors":"Derya Demirtaş Esmer, Emre Hafızoğlu, Murat Bardakçı, Erdem Özkan, Serhat Sekmek, Doğan Bayram, İrfan Karahan, Efnan Algın, Öznur Bal","doi":"10.1186/s13048-025-01960-4","DOIUrl":"10.1186/s13048-025-01960-4","url":null,"abstract":"<p><strong>Background: </strong>Advanced epithelial ovarian cancer (EOC) is commonly diagnosed at late stages, and despite improvements with neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS), prognosis remains poor. Body composition has emerged as an important determinant of treatment outcomes. Low muscle mass (LMM), particularly in obese patients with low muscle mass (OwLMM), may combine impaired functional reserve with adverse metabolic effects. However, its role in NACT outcomes in EOC remains unclear.</p><p><strong>Methods: </strong>In this retrospective study, 52 overweight or obese women with FIGO stage III-IV EOC treated with platinum-taxane-based NACT and IDS between 2019 and 2022 were analyzed. Skeletal muscle mass was assessed on baseline computed tomography scans at the third lumbar vertebra (L3), and the lumbar skeletal muscle index (LSMI) was calculated. Patients were classified as LMM or high muscle mass (HMM) using the cohort median cut-off. Patients with both obesity and LMM were categorized as OwLMM. Treatment response was evaluated using RECIST v1.1 criteria.</p><p><strong>Results: </strong>The median follow-up was 10.2 months (95% CI, 7.8-12.6). Median disease-free survival (DFS) from IDS was 19.3 months (95% CI, 8.5-30.1). OwLMM patients had lower objective response rates (46.7% vs. 62.2%, p = 0.02) and inferior disease control rates (80% vs. 100%, p = 0.03) compared with other groups. BMI or LMM alone showed no significant effect. Overall survival (OS) analysis was premature due to the short follow-up period.</p><p><strong>Conclusion: </strong>Low muscle mass, especially when combined with obesity, was associated with reduced NACT response and inferior disease control in advanced EOC. As sarcopenic obesity represents a key component of frailty in older adults, our findings support muscle mass assessment as a clinically relevant biomarker that may improve risk stratification and guide individualized therapy in geriatric oncology.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258321","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":"Ceramide: a pivotal lipid mediator shaping female reproductive homeostasis and pathophysiology.","authors":"Wujia Wang, FangYi Zhang, Lixuan Huang, Jie Qiao, Xinyu Qi","doi":"10.1186/s13048-026-02169-9","DOIUrl":"10.1186/s13048-026-02169-9","url":null,"abstract":"<p><p>Ceramide, a central hub in sphingolipid metabolism, serves as a critical bioactive signalling mediator that integrates lipid metabolism with multiple signalling pathways, primarily promoting autophagy and apoptosis. It influences female reproductive homeostasis and pathophysiology through multiple dimensions: altered ceramide levels have been observed in various reproductive disorders-such as polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI) and endometriosis (EM)-as well as across the female lifespan. These changes impact key processes including gonadotropin release, follicular development, and uterine microenvironment homeostasis. This review systematically summarizes the effects of ceramide on female fertility, highlighting its role as a pivotal entry point for understanding reproductive endocrine disorders in women. Modulating ceramide levels may represent a promising therapeutic strategy to enhance fertility and promote female reproductive health.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258274","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":"Stage-, dose- and course-dependent disruption of mice fetal ovarian development following prenatal dexamethasone exposure.","authors":"Lu Chen, Shan Jin, Zhaojun Wang, Abudukade Subinu, Fan Mo, Jing Huang, Hui Wang","doi":"10.1186/s13048-026-02158-y","DOIUrl":"10.1186/s13048-026-02158-y","url":null,"abstract":"<p><strong>Background: </strong>Dexamethasone, a synthetic glucocorticoid, is widely used during pregnancy to prevent preterm infant respiratory distress syndrome. While our prior work established that multiple courses of prenatal dexamethasone exposure (PDE) impair offspring ovarian function with transgenerational effects, the specific impacts of exposure stages, doses, and courses remain poorly defined.</p><p><strong>Materials and methods: </strong>Pregnant Kunming mice were treated with dexamethasone during mid-late gestation (GD14-15) or late gestation (GD16-17) with low/moderate/high doses, either as a single course or as two consecutive courses. Fetal ovaries were collected at GD18 to assess morphology, cell proliferation/apoptosis, steroidogenic markers, and oocyte-development genes; network toxicology was used to infer candidate pathways.</p><p><strong>Results: </strong>PDE disrupted fetal ovarian morphogenesis, characterized by premature germ-cell nest breakdown, reduced proliferation and increased apoptosis. PDE at different stages, doses and courses can increase ovarian steroid synthesis (SF1StARCYP11A1Hsd3bCYP19A1) while suppressing oocyte and folliculogenesis genes (NOBOXFiglαSohlh2Bmp15Gdf9). These effects are stage-, dose- and course-dependent, with the most obvious toxicity resulting from exposure in the mid-late stages of pregnancy, at high doses and in a single course. Network toxicology and qPCR revealed the NR3C1-MAPK14-IL6 axis: IL6 was positively correlated with proliferation and oocyte development markers, while NR3C1/MAPK14 was associated with apoptosis and steroidogenesis.</p><p><strong>Conclusions: </strong>This study provides experimental evidence for guiding clinical \"precision medicine\" and effectively assessing the risk of fetal ovarian developmental toxicity.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13495270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252008","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}