Journal of Ovarian Research最新文献

{"title":"Negligible serum anti-Müllerian hormone levels and successfully spontaneous pregnancy three times: a case report.","authors":"Yiman Fu, Baoyi Huang, Lin Ma","doi":"10.1186/s13048-025-01640-3","DOIUrl":"10.1186/s13048-025-01640-3","url":null,"abstract":"<p><strong>Background: </strong>Anti-Müllerian hormone (AMH) is a useful marker of ovarian reserve in reproductive-aged women. However, the predictive value of AMH for the occurrence of a spontaneous ongoing pregnancy has limits. We reported a patient with extreme low AMH achieved spontaneous conception three times.</p><p><strong>Case presentation: </strong>A 35-year-old woman, gravida 1, para 0, with a history of one miscarriage, presented with a one-year history of secondary infertility seeking reproductive assistance. Laboratory evaluation showed negligible (0.072 ng/mL or 0.514 pmol/L) AMH levels and ultrasound revealed reduced bilateral antral follicle count (AFC). She was diagnosed with diminished ovarian reserve (DOR) and counseled about her limited fertility prognosis. Despite recommendations for assisted reproductive techniques (ART), the patient pursued spontaneous conception. Two natural cycles and two ovulation induction cycles were conducted, utilizing recombinant follicle-stimulating hormone (FSH) with ovulation triggered by 8,000 IU of human chorionic gonadotropin (HCG). Remarkably, the patient successfully conceived three pregnancies and delivered four healthy children. In April 2022, she gave birth to a healthy boy weighing 3.17 kg via spontaneous vaginal delivery. In August 2023, she delivered another healthy boy weighing 3.80 kg via spontaneous vaginal delivery. Subsequently, in November 2024, she delivered healthy twins-one boy and one girl-via spontaneous vaginal delivery.</p><p><strong>Conclusions: </strong>This case underscores the clinical significance of specialized reproductive medicine intervention in achieving successful pregnancy outcomes in patients with rapidly declining and persistently low AMH levels. It highlights that even in cases of severely diminished ovarian reserve, natural conception is possible with expert guidance. Clinicians should exercise prudence when providing prognostic guidance regarding fertility among patients presenting with markedly diminished or undetectable AMH concentrations. The application of AMH measurement for fertility assessment in the general population still need to be clarified in well-designed prospective studies.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"57"},"PeriodicalIF":3.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11916997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657366","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":"Untargeted metabolomics reveals homogeneity and heterogeneity between physiological and pathological ovarian aging.","authors":"Lihua Zeng, Yunyi Liang, Lizhi Huang, Zu'ang Li, Manish Kumar, Xiasheng Zheng, Jing Li, Songping Luo, Ling Zhu","doi":"10.1186/s13048-025-01625-2","DOIUrl":"10.1186/s13048-025-01625-2","url":null,"abstract":"<p><strong>Background: </strong>Ovarian aging is the main cause of reduced reproductive life span, yet its metabolic profiles remain poorly understood. This study aimed to reveal the metabolic homogeneity and heterogeneity between physiological and pathological ovarian aging.</p><p><strong>Methods: </strong>Seventy serum samples from physiological ovarian aging participants, pathological ovarian aging participants (including diminished ovarian reserve (DOR), subclinical premature ovarian insufficiency (scPOI) and premature ovarian insufficiency (POI)), as well as healthy participants were collected and analyzed by untargeted metabolomics.</p><p><strong>Results: </strong>Five homogeneous differential metabolites (neopterin, menaquinone, sphingomyelin (SM) (d14:1/24:2), SM (d14:0/21:1) and SM (d17:0/25:1)) were found in both physiological and pathological ovarian aging. While five distinct metabolites, including phosphoglyceride (PC) (17:0/18:2), PC (18:2e/17:2), SM (d22:1/14:1), SM (d14:1/20:1) and 4-hydroxyretinoic acid were specific to pathological ovarian aging. Functional annotation of differential metabolites suggested that folate biosynthesis, ubiquinone and other terpenoid-quinone biosynthesis pathways, were mainly involved in the ovarian aging process. Meanwhile, dopaminergic synapses pathway was strongly associated with scPOI, vitamin digestion and absorption and retinol metabolism were associated with POI. Furthermore, testosterone sulfate, SM (d14:0/28:1), PC (18:0e/4:0) and 4-hydroxyretinoic acid, were identified as potential biomarkers for diagnosing physiological ovarian aging, DOR, scPOI, and POI, respectively. Additionally, SM (d14:1/24:2) strongly correlated with both physiological and pathological ovarian aging. 4-hydroxyretinoic acid was strongly correlated with pathological ovarian aging.</p><p><strong>Conclusions: </strong>Metabolic homogeneity of physiological and pathological ovarian aging was related to disorders of lipid, folate, ubiquinone metabolism, while metabolic heterogeneity between them was related to disorders of lipid, vitamin and retinol metabolism.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"56"},"PeriodicalIF":3.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649322","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":"Causal relationships of gut microbiota and blood metabolites with ovarian cancer and endometrial cancer: a Mendelian randomization study.","authors":"Jinyan Chen, Xuejun Chen, Jiong Ma","doi":"10.1186/s13048-025-01630-5","DOIUrl":"10.1186/s13048-025-01630-5","url":null,"abstract":"<p><strong>Objectives: </strong>The study aimed to investigate the causal relationships of gut microbiota (GM), ovarian cancer (OC), endometrial cancer (EC), and potential metabolite mediators using Mendelian randomization (MR) analysis.</p><p><strong>Methods: </strong>Bidirectional two-sample MR analysis and reverse MR analysis of GM on OC/EC were employed to determine the causal effects of GM on OC/EC and the mediating role of blood metabolites in the relationship between GM and OC/EC, with results validated through sensitivity analysis.</p><p><strong>Results: </strong>We identified 6 pathogenic bacterial taxa associated with OC, including Euryarchaeota, Escherichia-Shigella, FamilyXIIIAD3011group, Prevotella9, and two unknown genera. Christensenellaceae R.7group, Tyzzerella3, and Victivallaceae were found to be protective against OC. The increase in EC risk was positively associated with Erysipelotrichia, Erysipelotrichaceae, Erysipelotrichales, and FamilyXI. Dorea, RuminococcaceaeUCG014, and Turicibacter exhibited a negative correlation with the EC risk. A total of 26 and 19 blood metabolites related to GM were identified, showing significant correlations with OC and EC, respectively. Cytosine was found to be an intermediate metabolite greatly associated with EC and FamilyXI. In reverse MR analysis, the FamilyXIIIAD3011group exhibited a significant bidirectional causal relationship with OC.</p><p><strong>Conclusion: </strong>Our study revealed causal relationships of GM and intermediate metabolites with OC/EC, providing new avenues for understanding OC/EC and developing effective treatment strategies.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"54"},"PeriodicalIF":3.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625129","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":"miR-34a-5p modulation of polycystic ovary syndrome via targeting the NOTCH signaling pathway.","authors":"Kexin Zhang, Xiaomeng Wang, Fang Liu, Hong Lin, Yan Wang, Min Zhao, Xiaofei Wang, Yijing Chu, Lin Xu","doi":"10.1186/s13048-025-01623-4","DOIUrl":"10.1186/s13048-025-01623-4","url":null,"abstract":"<p><strong>Purpose: </strong>Polycystic ovary syndrome (PCOS) is currently recognized as a condition that affects several systems in the body, including the reproductive, endocrine, and cardiovascular systems. Prevalent among teenagers and women of reproductive age. Prior research has demonstrated an elevation of miR-34a-5p within the follicular fluid (FF) of women of PCOS. Despite this, the precise mechanisms through which miR-34a-5p influences granulosa cells (GC) development and function remain poorly characterized.</p><p><strong>Methods: </strong>Therefore, this study investigates the involvement and pathogenic mechanisms of miR-34a-5p within GCs in the context of PCOS. The human granulosa-like tumor cell line (KGN) got transfected at a control, as well as a miR-34a-5p mimic and inhibitor, respectively. Monitor cellular proliferation in each experimental group. The experimental methods included RT-qPCR, CCK8, flow cytometry and western blotting. Also, the interaction between miR-34a-5p and the particular sequence of JAG1 has been verified using the dual luciferase assay. Further investigation of the connection involving miR-34a-5p and the Notch signaling pathway was conducted using bioinformatics analysis and experimental methods.</p><p><strong>Results: </strong>The results demonstrated that miR-34a-5p expression was significantly elevated in the serum(p<0. 0001)and FF (p = 0. 0402) of PCOS, whereas its expression in GCs (p = 0. 5522) showed no significant variation. Overexpressing miR-34a-5p caused a decrease in the rate at which KGN cells multiplied and an increase in programmed cell death. Conversely, inhibiting miR-34a-5p resulted in an increase in cell growth and a decrease in programmed cell death. Bioinformatics analysis and experimental results further demonstrated thatmiR-34a-5p interacts with the 3'UTR region of JAG1, leading to a negative regulation of the Jagged1-Notch signaling pathway.</p><p><strong>Conclusion: </strong>In summary, the miR-34a-5p molecule inhibits the growth of GCs as well as triggers programmed cell death by regulating the Jagged1-Notch signaling pathway. Silencing miR-34a-5p prevents dysfunction in GCs. Our analysis implies that miR-34a-5p is a new molecular site to treat PCOS.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"55"},"PeriodicalIF":3.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625144","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":"Follicular metabolic dysfunction, oocyte aneuploidy and ovarian aging: a review.","authors":"Die Wu, Chuanming Liu, Lijun Ding","doi":"10.1186/s13048-025-01633-2","DOIUrl":"10.1186/s13048-025-01633-2","url":null,"abstract":"<p><p>With the development of modern society and prolonged education, more women choose to delay their childbearing age, which greatly increases the number of women aged older than 35 years with childbearing needs. However, with increasing age, the quantity and quality of oocytes continue to fall, especially with increasing aneuploidy, which leads to a low in vitro fertilization (IVF) success rate, high abortion rate and high teratogenesis rate in assisted reproduction in women with advanced maternal age. In addition to genetics and epigenetics, follicular metabolism homeostasis is closely related to ovarian aging and oocyte aneuploidy. Glucose, lipid, and amino acid metabolism not only provide energy for follicle genesis but also regulate oocyte development and maturation. This review focuses on the relationships among follicular metabolism, oocyte aneuploidy, and ovarian aging and discusses potential therapeutic metabolites for ovarian aging.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"53"},"PeriodicalIF":3.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615769","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":"Enhancing understanding of endometrial function in patients with PCOS: clinical and immunological insights.","authors":"Yaxin Guo, Jingfei Yang, Hong Chen, Yueping Zhou, Yan Yang, Biao Wang, Luyang Zha, Dijia Bai, Wenxuan Li, Xiaojuan Tang, Zishui Fang, Fei Li, Lei Jin","doi":"10.1186/s13048-025-01638-x","DOIUrl":"10.1186/s13048-025-01638-x","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the pregnancy and perinatal outcomes of different phenotypes of polycystic ovary syndrome (PCOS) patients during the frozen embryo transfer (FET) cycles. Additionally, to analyze the T cell balance in the endometrium of PCOS patients and explore its relationship with various PCOS phenotypes.</p><p><strong>Design: </strong>Retrospective cohort study.</p><p><strong>Setting: </strong>A single academically affiliated reproductive medicine center.</p><p><strong>Patients: </strong>21,074 FET cycles were included and divided into two groups based on the diagnosis of PCOS. Patients with PCOS were further categorized into four phenotypic groups: PCOM + HA + OA, PCOM + HA, PCOM + OA, and HA + OA. Endometrial biopsies from 21 PCOS patients and 26 controls were obtained to analyze T cell subsets.</p><p><strong>Methods: </strong>Pregnancy and perinatal outcomes, as well as T cell subset abundance were compared between women with and without PCOS. Multiple logistic regression models were employed to adjust for confounding factors impacting pregnancy-related outcomes. Flow cytometry was utilized to analyze the abundance of T cell subsets.</p><p><strong>Main outcome measures: </strong>Pregnancy and perinatal outcomes were assessed. T cell subsets including CD4⁺CD8^-T cells, CD4^-CD8⁺T cells, Th1, Th2, Th17 and Treg cells in the endometrium were determined by flow cytometry.</p><p><strong>Results: </strong>There was a significantly increased incidence of miscarriage, hypertensive disorders of pregnancy (HDP), preterm birth (PTB), and even fetal malformations across different phenotypes of PCOS women, especially those with the hyperandrogenic phenotype. Th1 cells decreased while Th2 cells increased significantly in the PCOS endometrium.</p><p><strong>Conclusions: </strong>The unfavorable pregnancy and perinatal outcomes in FET cycles and T cell imbalance both suggest the endometrial dysfunction of PCOS patients, especially those with the hyperandrogenic phenotype.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"52"},"PeriodicalIF":3.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615768","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":"Intrinsic differences in mTOR activity mediates lineage-specific responses to cyclophosphamide in mouse and human granulosa cells.","authors":"Shiqian Xu, Yerong Ma, Yinli Zhang, Hanqi Ying, Xiaomei Tong, Weijie Yang, Yibin Pan, Yan Rong, Yangyang Dai, Songying Zhang, Peidong Han","doi":"10.1186/s13048-025-01627-0","DOIUrl":"10.1186/s13048-025-01627-0","url":null,"abstract":"<p><strong>Background: </strong>Cyclophosphamide (CTX) often induces oocyte and granulosa cell injury, leading to fertility loss in young female cancer survivors. Deciphering the mechanisms underlying follicular cell injury could offer novel insights into fertility preservation. Granulosa cells represent the most abundant cell type within the follicles and can be generally categorized as cumulus granulosa cells (CGCs) and mural granulosa cells (MGCs). Despite the essential roles of granulosa cells in supporting ovarian function in physiological conditions, their distinct lineage-specific responses to CTX remains elusive.</p><p><strong>Results: </strong>Here, we performed a genome-wide transcriptome analysis of murine mural and cumulus granulosa cells before and after CTX administration. Compared with MGCs, CGCs exhibited higher basal mammalian target of rapamycin (mTOR) activity and an increased DNA damage response post-injury. Pharmacological mTOR suppression or RNA interference-mediated gene silencing of Raptor, a key component of the mTORC1 complex, significantly reduced DNA damage in granulosa cells induced by 4-HC, an activated form of CTX. Notably, by examining human granulosa cells in response to 4-HC, our results uncovered a conserved role of mTOR inhibition in ovarian protection.</p><p><strong>Conclusions: </strong>Taken together, our findings reveal that intrinsic variations in mTOR activity in CGC and MGC lineages determine their differential responses to CTX. Targeting this signaling pathway may prove beneficial in mitigating CTX-induced granulosa cell apoptosis and protecting against ovarian injury.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"49"},"PeriodicalIF":3.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605227","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":"Gengnianchun formula ameliorates insulin resistance-induced diminished ovarian reserve via the estrogen signaling pathway: evidence from network pharmacology and experimental validation.","authors":"Yanqiu Rao, Jun Li, Ting Xu, Lingyun Gao, Wenjun Wang","doi":"10.1186/s13048-025-01632-3","DOIUrl":"10.1186/s13048-025-01632-3","url":null,"abstract":"<p><strong>Background: </strong>Diminished ovarian reserve (DOR), a major cause of female infertility, is closely linked to insulin resistance (IR). Traditional Chinese Medicine (TCM) approaches, such as the Gengnianchun (GNC) formula, focus on restoring ovarian function by improving IR and regulating hormonal balance. Despite GNC's demonstrated efficacy, its precise therapeutic mechanisms remain unclear.</p><p><strong>Objective: </strong>This study aims to elucidate the mechanisms by which GNC ameliorates IR-induced DOR through comprehensive pharmacological and experimental validation.</p><p><strong>Methods: </strong>The study combined Liquid chromatograph mass spectrometer (LC-MS), ultra-performance liquid chromatography (UPLC-TOF-MS/MS), network pharmacology, and molecular docking to identify active components and key therapeutic targets of GNC. Functional enrichment analyses (GO and KEGG) and molecular docking studies were performed. A high-fat diet-induced mouse model of IR-DOR was established, followed by GNC treatment at varying doses. Therapeutic effects were evaluated via qRT-PCR, western blot, immunofluorescence, and histological analysis.</p><p><strong>Results: </strong>GNC contains 219 active ingredients targeting 53 genes associated with IR-induced DOR. KEGG analysis revealed the estrogen signaling pathway as a key mechanism. High-dose GNC significantly improved IR and ovarian reserve by increasing AKT1, ESR1, and ESR2 expression, as confirmed by qRT-PCR, western blot and immunofluorescence analysis. These findings indicate that GNC enhances insulin sensitivity, promotes follicular development, and restores ovarian function.</p><p><strong>Conclusions: </strong>This study demonstrates for the first time that GNC alleviates IR-induced DOR by modulating the estrogen signaling pathway and activating key molecular targets. These results provide a foundation for clinical research and the development of novel therapeutic strategies for DOR.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"51"},"PeriodicalIF":3.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605226","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":"Causal association between metabolic syndrome and ovarian dysfunction: a bidirectional two-sample mendelian randomization.","authors":"Ying He, Yanling Wei, Haixia Liang, Yi Wan, Ying Zhang, Jianfang Zhang","doi":"10.1186/s13048-025-01614-5","DOIUrl":"10.1186/s13048-025-01614-5","url":null,"abstract":"<p><strong>Background: </strong>The relationship between Metabolic Syndrome (MetS) and ovarian dysfunction has been widely reported in observational studies, yet it remains not fully understood. This study employs genetic prediction methods and utilizes summary data from genome-wide association studies (GWAS) to investigate this causal link.</p><p><strong>Methods: </strong>We employed a bidirectional two-sample Mendelian Randomization (MR) analysis utilizing MetS and ovarian dysfunction summary data from GWAS. Inverse variance weighted (IVW) was employed as the primary MR method, supplemented by Weighted Median, Weighted Mode, and MR-Egger methods. The robustness of the results was further assessed through sensitivity analyses including MR-Egger regression, MR-PRESSO, Cochran's Q, and leave-one-out test.</p><p><strong>Results: </strong>Our MR analysis identified a causal relationship between genetically determined insulin resistance (OR = 0.26, 95% CI: 0.08-0.89, P = 0.03), waist circumference (OR = 2.14, 95% CI: 1.45-3.15, P < 0.001), BMI (OR = 2.1, 95% CI: 1.56-2.83, P < 0.001) and ovarian dysfunction. Conversely, reverse MR analysis confirmed causal effects of ovarian dysfunction on metabolic syndrome (OR = 0.98, 95% CI: 0.97-0.99, P < 0.001) and waist circumference (OR = 0.99, 95% CI: 0.98-0.99, P = 0.02). The results of MR-Egger regression test indicated that the whole analysis was not affected by horizontal pleiotropy. Additionally, the MR-PRESSO test identified outliers in SNPs, but after removal of outliers, results remained unchanged.</p><p><strong>Conclusion: </strong>This study reveals a bidirectional causal connection between metabolic syndrome and ovarian dysfunction via genetic prediction methods. These findings are crucial for advancing our understanding of the interactions between these conditions and developing strategies for prevention and treatment.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"50"},"PeriodicalIF":3.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605225","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":"Link between iron-mediated lipid peroxidation and polycystic ovary syndrome (PCOS): exploring the genes underlying iron regulatory mechanism.","authors":"Nighat Hayat, Zertashia Akram, Nayab Khalid, Nasreen Rehmat Ullah, Tehmina Mazhar","doi":"10.1186/s13048-024-01562-6","DOIUrl":"10.1186/s13048-024-01562-6","url":null,"abstract":"<p><strong>Objective: </strong>Mechanism underlying the etiology of polycystic ovary syndrome (PCOS) is still debatable. Present study explores the link between iron-mediated ferroptosis and PCOS.</p><p><strong>Methodology: </strong>Blood samples were collected from 150 PCOS females along with healthy controls. Expression analysis of FTH1, NCOA4, GPX4, HAMP, A2M and HP genes was estimated by RT-qPCR. Serum was used for estimation of lipid peroxidation, peroxidase enzyme, ferritin and total protein.</p><p><strong>Results: </strong>Relative expression of FTH1 (P < 0.05), HAMP (P < 0.01), GPX4, A2M, HP (P < 0.001) was downregulated and NCOA4 (P < 0.001) was upregulated in PCOS group compared to control. A significant difference was observed in mRNA expression of selected genes when ≤ 30year age group PCOS was compared to > 30year age PCOS group and their respective controls. Deregulation of gene expression was prominent in PCOS group with obese and overweight BMI compared to underweight and normal BMI group. Menstrual cycle length and marital status of PCOS females had no significant association with selected gene expression. Expression deregulation in targeted genes was observed in PCOS patients with complaints of either diabetes, high blood pressure or both. Increased level of lipid peroxidation, serum ferritin and total protein, while decreased peroxidase activity was observed in PCOS group (P < 0.001) compared to control.</p><p><strong>Conclusion: </strong>The present study postulated the role of iron overload in trigger of ferroptosis following elevated lipid peroxidation and low peroxidase activity. Moreover, unveil the association of genes related to iron-regulating metabolism with etiology of underlying PCOS mechanism.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"48"},"PeriodicalIF":3.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586041","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}