{"title":"Dissecting the causal effects of interleukin receptor-related factors and the risk of developing endometriosis: a two-sample Mendelian randomization study.","authors":"Si-Ji Lv, Qing Yuan, Shan-Shan Zong, Lei Ye","doi":"10.1080/09513590.2025.2512837","DOIUrl":"https://doi.org/10.1080/09513590.2025.2512837","url":null,"abstract":"<p><p>This study investigates the causal associations between interleukin receptor-related factors and the development of endometriosis, as their etiology and pathophysiology remain largely unknown. A two-sample Mendelian randomization (MR) approach was employed to analyze genetic variants associated with interleukin receptor related factors as instrumental variables (IVs). The F-values have to be > 10 to exclude weak instrumental bias. The primary analysis was conducted using the inverse variance weighted (IVW) method, with confirmation using the MR-Egger, weighted median (WM), simple mode, and weighted mode methods. Sensitivity analyses were performed to ensure robustness, including tests for heterogeneity, pleiotropy, and leave-one-out. Multivariable MR (MVMR) analysis was used to assess the direct and mediated effects of immune cells. The results indicated significant causal associations between interleukin receptor factors prot-a-1542 (IL-6Rβ), prot-a-1530 (IL-3Rα), and prot-b-38 (IL-1RL1) and endometriosis. Reverse MR analysis showed that endometriosis did not significantly affect prot-a-1530 or prot-b-38. After adjusting for confounders like body mass index and smoking, these factors retained their significance. Additionally, immune cells(ebi-a-GCST90001951) were found to mediate the relationship between prot-b-38 and endometriosis, with an indirect effect accounting for approximately 6.38% of the total effect. This study provides new insights into endometriosis mechanisms involving specific interleukin receptor factors.</p>","PeriodicalId":12865,"journal":{"name":"Gynecological Endocrinology","volume":"41 1","pages":"2512837"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"SIRT5 regulates granulosa cell proliferation and apoptosis in polycystic ovarian syndrome <i>via</i> desuccinylation of GLI1.","authors":"Yiwen Zhang, Fangfang He, Ning Cai, Guanmei Chen, Yinyin Wang, Weiwei Bai, Peng Guo","doi":"10.1080/09513590.2025.2515516","DOIUrl":"https://doi.org/10.1080/09513590.2025.2515516","url":null,"abstract":"<p><p>Polycystic ovarian syndrome (PCOS) is a major cause of infertility. Succinylation is involved in disease processes; however, its role in PCOS remains unknown. This study aimed to analyze the effect of desuccinylase SIRT5 on granulosa cell phenotype and the molecular mechanism. The levels of succinylation-related enzymes were measured using reverse transcription-quantitative polymerase chain reaction and immunoblotting. Cell proliferation was evaluated using MTT and colony formation assays, and apoptosis was assessed using flow cytometry. The succinylation was analyzed using immunoprecipitation, cycloheximide chase assay, and immunoblotting. The results showed that SIRT5 was highly expressed in PCOS, and knockdown of SIRT5 promoted granulosa cell proliferation and inhibited apoptosis, as well as activated the SHH pathway. Moreover, silencing of SIRT5 promoted GLI1 succinylation at lysine (K)232 site and thereby suppressed its degradation. GLI1 knockdown reversed the promotion of proliferation and the inhibition of apoptosis caused by SIRT5 knockdown. Besides, SIRT5 knockdown attenuated ovarian dysfunction and inhibited apoptosis in PCOS rats by increasing GLI expression. In conclusion, silencing of SIRT5 facilitates granulosa cell proliferation and impedes apoptosis by succinylation of GLI1 at K232 site, and thus attenuates PCOS. The findings suggest that SIRT5 may be a promising target for PCOS therapy.</p>","PeriodicalId":12865,"journal":{"name":"Gynecological Endocrinology","volume":"41 1","pages":"2515516"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hsa_circ_0020491 promotes polycystic ovary syndrome by interacting with IGF2BP2 through regulation of granular cell autophagy and mitochondrial dysfunction.","authors":"XiaLing Huang, Fen Yu","doi":"10.1080/09513590.2025.2536579","DOIUrl":"https://doi.org/10.1080/09513590.2025.2536579","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women, yet its underlying mechanisms remain incompletely understood. This study investigated the role of hsa_circ_0020491 in PCOS pathogenesis, focusing on granulosa cells (GCs). Analysis of GCs from PCOS patients and controls revealed significant upregulation of both hsa_circ_0020491 and IGF2BP2, with their expression levels positively correlated. In a dihydrotestosterone (DHT)-treated KGN cell model of PCOS, silencing either circ_0020491 or IGF2BP2 mitigated autophagy dysregulation and mitochondrial dysfunction, evidenced by altered autophagy-related proteins, mitochondrial membrane potential, ATP levels, mtDNA content, and reactive oxygen species. Mechanistically, circ_0020491 binds to and stabilizes IGF2BP2, amplifying its effects. Overexpression of IGF2BP2 counteracted the improvements induced by circ_0020491 knockdown. In vivo, a dehydroepiandrosterone (DHEA)-induced PCOS mouse model confirmed that circ_0020491 suppression attenuated disease progression, improved mitochondrial function, and reduced excessive autophagy. These findings demonstrate that hsa_circ_0020491 exacerbates PCOS by interacting with IGF2BP2 to disrupt autophagy and mitochondrial homeostasis in GCs, offering a potential therapeutic target.</p>","PeriodicalId":12865,"journal":{"name":"Gynecological Endocrinology","volume":"41 1","pages":"2536579"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rossella E Nappi, Angelo Cagnacci, Costantino Di Carlo, Alessandro D Genazzani, Paola Villa, Tommaso Simoncini
{"title":"Targeting vasomotor symptoms with the new drug fezolinetant - an expert overview.","authors":"Rossella E Nappi, Angelo Cagnacci, Costantino Di Carlo, Alessandro D Genazzani, Paola Villa, Tommaso Simoncini","doi":"10.1080/09513590.2025.2526560","DOIUrl":"https://doi.org/10.1080/09513590.2025.2526560","url":null,"abstract":"<p><p>Menopause is an inevitable event in the life of women who live long enough to reach this milestone. The experience of menopause varies amongst individuals. Menopause has a negative impact on women's life and is associated with symptoms including vasomotor symptoms (VMS), such as hot flushes and night sweats, sleep disturbances and low mood. VMS are bothersome and may have a long duration. Menopause hormone therapy (MHT) is recommended in women with symptoms; however, its use is limited. The recent approval of fezolinetant offers a new therapeutic option for women who suffer from VMS and are unsuitable or averse to MHT. Fezolinetant is a precision drug as it targets the pathological mechanism of VMS showing some effect also on sleep disturbances. Given how variable the experience of menopause is, it is important to offer individualized treatment options to women who suffer from menopause-related symptoms and let them be part of the shared decision making.</p>","PeriodicalId":12865,"journal":{"name":"Gynecological Endocrinology","volume":"41 1","pages":"2526560"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guangzhong Jiao, Jinhao Xing, Zhaoli Du, Hongchu Bao, Xiaoyan Liu
{"title":"Biallelic mutations in CDC20 cause female infertility due to oocyte maturation abnormality.","authors":"Guangzhong Jiao, Jinhao Xing, Zhaoli Du, Hongchu Bao, Xiaoyan Liu","doi":"10.1080/09513590.2025.2451672","DOIUrl":"10.1080/09513590.2025.2451672","url":null,"abstract":"<p><p>Oocyte maturation arrest (OMA) may occur at different stages, including the germinal vesicle (GV), metaphase I (MI), and metaphase II (MII). A total maturation arrest of human oocytes is rarely observed during <i>in vitro</i> fertilization (IVF). We have identified a case of infertile female for whom all oocytes fail to mature and are arrested at MI. Whole-exome sequencing revealed a compound heterozygous mutant (c.533C > A: p.Val458Ala; c.1373T > C: p.Ala178Glu) in cell division cycle 20 (<i>CDC20</i>). Through rigorous validation using Sanger sequencing technology, both of her parents have been confirmed as genetic carriers of these specific mutations. Based on the three-dimensional (3D) structures of the CDC20 protein used to assess the effect of the mutant, the mutant causes a change in hydrogen bond in the protein structure, which may affect the stability of the mutant protein. Previous studies have firmly established CDC20 as a pivotal member of the cell cycle regulation family, playing an indispensable role in the transition from metaphase to anaphase during cell division. Our findings not only broaden the current understanding of <i>CDC20</i> gene mutations but also profoundly illuminate how these mutations serve as potential genetic mechanisms underlying the arrest of oocyte maturation.</p>","PeriodicalId":12865,"journal":{"name":"Gynecological Endocrinology","volume":"41 1","pages":"2451672"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ye Tian, Fang Li, Tuo Kuang, Xiangning Li, Xin Zhou, Xiaohong Bai
{"title":"The oxylipins profile and their associations with embryo quality of women with polycystic ovary syndrome: a prospective cohort study.","authors":"Ye Tian, Fang Li, Tuo Kuang, Xiangning Li, Xin Zhou, Xiaohong Bai","doi":"10.1080/09513590.2025.2541658","DOIUrl":"https://doi.org/10.1080/09513590.2025.2541658","url":null,"abstract":"<p><p>This study was aim to investigate the oxylipins profile in the follicular fluid (FF) of women with PCOS and examine their associations with embryo quality.</p><p><p>We conducted a targeted lipidomic study involving sixty-two cases of PCOS and age-matched controls (Cohort 1) <i>via</i> UHPLC-MS. Cohort 2 included sixty cases of PCOS and age-and-BMI-matched controls who were recruited for validation <i>via</i> targeted lipidomics. The associations between these oxylipins and baseline hormones as well as embryo quality in PCOS patients were analyzed.</p><p><p>A total of 59 oxylipins were identified in the FF of PCOS patients. In the FF of PCOS patients in Cohort 1, the level of 16(17)-EpDPE, a product derived from docosahexaenoic acid (DHA), was greater than that in the control group, even after adjustment for age, BMI and multiple comparisons (<i>p</i> < 0.001, adjusted <i>p</i> = 0.032). An increased concentration of 16(17)-EpDPE in women with PCOS was further validated in Cohort 2 (<i>p</i> < 0.001, adjusted <i>p</i> = 0.044). In addition, compared with the control group, the PCOS group in Cohort 2 presented significantly lower levels of eicosapentaenoic acid (EPA)-derived oxylipins (18-HEPE), DHA-derived oxylipins (4-HDoHE, 16-HDoHE), linoleic acid(LA)-derived oxylipins (12,13-EpOME, 13-HODE and 9-oxoODE), and dihomo-gamma-linolenic acid(DGLA)-derived oxylipins (15-HETrE). Correlation analyses between oxylipin metabolites and clinical features revealed that 16(17)-EpDPE was negatively associated with the number of D3 good-quality embryos and positively associated the blood lymphocyte count. Three LA-derived oxylipins were associated with the serum AMH and leptin levels in the FF.</p><p><p>Our study revealed distinct metabolic signatures in women with PCOS and identified 16(17)-EpDPE as a novel biomarker for PCOS and their D3 good-quality embryos count.</p>","PeriodicalId":12865,"journal":{"name":"Gynecological Endocrinology","volume":"41 1","pages":"2541658"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hyaluronic acid in the management of postmenopausal vaginal atrophy: from moisturizer to mucosal regenerator.","authors":"Santiago Palacios","doi":"10.1080/09513590.2025.2545368","DOIUrl":"10.1080/09513590.2025.2545368","url":null,"abstract":"","PeriodicalId":12865,"journal":{"name":"Gynecological Endocrinology","volume":"41 1","pages":"2545368"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144872827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Youzhu Li, Yuanyuan Ye, Hengyuan Zhang, Ye Yang, Ningqing Zhang, Hong Gao, Rongfeng Wu
{"title":"MiR-19b-3p inhibits cell viability and proliferation and promotes apoptosis by targeting IGF1 in KGN cells.","authors":"Youzhu Li, Yuanyuan Ye, Hengyuan Zhang, Ye Yang, Ningqing Zhang, Hong Gao, Rongfeng Wu","doi":"10.1080/09513590.2024.2425318","DOIUrl":"10.1080/09513590.2024.2425318","url":null,"abstract":"<p><strong>Background: </strong>Endometriosis (EM) is a major cause of infertility, but the pathogenesis and mechanisms are not yet fully elucidated. MiR-19b-3p is involved in many diseases, but its functional role in EM-associated infertility remains unexplored. This study aimed to examine miR-19b-3p abundance and IGF1 concentration in cumulus cells (CCs) and follicular fluid of EM-associated infertility patients, and to investigate the potential role of miR-19b-3p in KGN cells by identifying its target and elucidating the underlying mechanisms.</p><p><strong>Results: </strong>The results from the case-control study indicated that, compared to the control group consisting of patients with tubal infertility, patients with EM-associated infertility exhibited a lower percentage of mature oocytes. MiR-19b-3p level was elevated in CCs from EM-associated infertility patients. IGF1 was identified as a direct target of miR-19b-3p and was negatively regulated by miR-19b-3p in KGN cells. Overexpression of miR-19b-3p significantly inhibited cell viability and proliferation, promoted apoptosis, and arrested the cell cycle at G0/G1 phase in KGN cells. The effects of miR-19b-3p were reversed by co-transfection of IGF1, and the biological effects of miR-19b-3p in KGN cells were mediated by IGF1. Additionally, miR-19b-3p targeted IGF1 to down-regulate AKT phosphorylation and participate in the apoptotic pathway in KGN cells.</p><p><strong>Conclusions: </strong>This study demonstrates that miR-19b-3p level is elevated in CCs and IGF1 concentration is decreased in follicular fluid in patients with EM-associated infertility. MiR-19b-3p regulates the biological effects of KGN cells by targeting IGF1.</p>","PeriodicalId":12865,"journal":{"name":"Gynecological Endocrinology","volume":"40 1","pages":"2425318"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu-Xin Jin, Hang-Qi Hu, Jia-Cheng Zhang, Xi-Yan Xin, Yu-Tian Zhu, Hao-Lin Zhang, Rui-Wen Fan, Yang Ye, Dong Li
{"title":"Research status of polycystic ovary syndrome treatment: a mini review and a bibliometric analysis from 2010 to 2023.","authors":"Yu-Xin Jin, Hang-Qi Hu, Jia-Cheng Zhang, Xi-Yan Xin, Yu-Tian Zhu, Hao-Lin Zhang, Rui-Wen Fan, Yang Ye, Dong Li","doi":"10.1080/09513590.2024.2405098","DOIUrl":"https://doi.org/10.1080/09513590.2024.2405098","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in premenopausal women, often linked to abdominal obesity, insulin resistance, and metabolic issues. With its heterogeneous nature, PCOS treatment should be tailored to individual symptoms and patient preferences. This study examines collaboration networks among countries, institutions, authors, references, and journals related to PCOS treatment.</p><p><strong>Methods: </strong>Web of Science data was analyzed using VOSviewer and CiteSpace for bibliometric visualization. Chinese and Western medicine treatments for PCOS were reviewed, emphasizing symptom-targeted solutions.</p><p><strong>Results: </strong>Data from 4682 records authored by 400 individuals from 515 institutes in 62 countries revealed China as the leading contributor. Notable authors include Monash University and Richard S. Legro. Common research themes include adipocytes, inflammation, insulin sensitivity, oxidative stress, and the gut microbiome. Tailoring treatment to individual needs is essential, focusing on hyperandrogenism, ovulation, and insulin resistance, with lifestyle counseling to address obesity.</p><p><strong>Conclusion: </strong>This bibliometric analysis provides valuable insights into the research status of PCOS treatment. China has made significant contributions, and complementary and alternative therapies, such as traditional Chinese medicine and acupuncture, have also shown beneficial effects recently. The research on inflammation, oxidative stress, and the gut microbiome may provide new targets and strategies for the treatment of PCOS. The recognition of the metabolic problems in PCOS patients facilitates the formulation of more personalized treatment plans to improve the prognosis of patients.</p>","PeriodicalId":12865,"journal":{"name":"Gynecological Endocrinology","volume":"40 1","pages":"2405098"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142284450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Statement of Retraction: The impact of letrozole on oocyte quality in assisted reproductive technology (ART); a randomized double-blind clinical trial.","authors":"","doi":"10.1080/09513590.2024.2419765","DOIUrl":"https://doi.org/10.1080/09513590.2024.2419765","url":null,"abstract":"","PeriodicalId":12865,"journal":{"name":"Gynecological Endocrinology","volume":"40 1","pages":"2419765"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}