Human reproduction open最新文献

{"title":"Endometrial compaction shows no association with improved pregnancy outcomes in hormonal replacement frozen-thawed embryo transfer: an analysis of over 16 000 cases.","authors":"Peipei Pan, Chang Liu, Shiyi Lin, Haiqing Wang, Xia Chen, Haiyan Yang, Xuefeng Huang, Huan Zhang, Yili Teng","doi":"10.1093/hropen/hoaf039","DOIUrl":"10.1093/hropen/hoaf039","url":null,"abstract":"<p><strong>Study question: </strong>Is there an association between changes in endometrial thickness (EMT) following progesterone administration and pregnancy outcomes in frozen-thawed embryo transfers (FETs) at Day 3 (D3) and blastocyst stages?</p><p><strong>Summary answer: </strong>Endometrial compaction is not associated with better pregnancy outcomes.</p><p><strong>What is known already: </strong>Previous studies have shown conflicting results on the impact of EMT changes on FET outcomes.</p><p><strong>Study design size duration: </strong>This study was a single-center retrospective cohort analysis of FETs from 1 January 2018 to 31 December 2022. A total of 9390 D3 FETs and 7063 blastocyst FETs were included during this period.</p><p><strong>Participants/materials setting methods: </strong>D3 FETs and blastocyst FETs were divided into three groups: compaction group, non-change group, and expansion group. The impact of EMT changes after progesterone administration on HCG-positive, pregnancy, ongoing pregnancy, live birth, and pregnancy loss rates were analyzed for D3 and blastocyst FETs. EMT on the progesterone administration day (defined as EMT1) and on embryo transfer (ET)day (defined as EMT2) was measured exclusively by transvaginal ultrasound. Inverse probability weighting (IPW) and stratified logistic regressions were conducted to reduce the effects of confounding factors.</p><p><strong>Main results and the role of chance: </strong>After IPW adjustment, in D3 FETs, women with compacted endometrium had the lowest HCG-positive rates (<i>P </i>= 0.012), clinical pregnancy rates (<i>P </i>< 0.001), ongoing pregnancy rates (<i>P </i>< 0.001), and live birth rates (LBRs) (<i>P </i>< 0.001) among the three groups. Among HCG-positive cases, the compaction group had the highest ectopic pregnancy rates (3.5% vs 2.6% vs 1.6%; <i>P </i>= 0.015) and the lowest LBRs (65.8% vs 68.3% vs 71.4%; <i>P </i>= 0.018). Univariate logistic regressions found that LBRs were weakly associated with compacted endometrium [odds ratio (OR) 0.831, 95% CI: 0.696-0.993]. Logistic regressions with IPW revealed that the compaction group was not associated with higher odds of pregnancy outcomes, including HCG positive, clinical pregnancy, ongoing pregnancy, ongoing pregnancy, and live births compared to the non-change group. In contrast, the expansion group was associated with higher odds of live birth per ETs (OR 1.166, 95% CI: 1.070-1.271; <i>P </i>= 0.001), and live birth per HCG-positive cases (OR 1.160, 95% CI: 1.028-1.309; <i>P </i>= 0.016). In blastocyst FETs, women with compacted endometrium had the lowest HCG-positive rates (<i>P </i>= 0.001) and clinical pregnancy rates (<i>P </i>= 0.031). Logistic regressions with IPW adjustment found that compaction group was associated with lower odds of HCG positive (OR 0.813, 95% CI: 0.668-0.989, <i>P </i>= 0.039) compared to the non-change group. Additionally, LBRs increased with the rising change ratios of EMT after progeste","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf039"},"PeriodicalIF":8.3,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variability and implications of recurrent implantation failure definitions used in the scientific literature: a systematic review.","authors":"Jessica K Lu, Yin Jun Law, Ning Zhang, Evangelia T Katsika, Efstratios M Kolibianakis, Christos A Venetis","doi":"10.1093/hropen/hoaf033","DOIUrl":"10.1093/hropen/hoaf033","url":null,"abstract":"<p><strong>Study question: </strong>How is recurrent implantation failure (RIF) defined in published literature and what is the prognostic agreement of these definitions with recently introduced RIF criteria by ESHRE?</p><p><strong>Summary answer: </strong>RIF definitions used in current clinical studies are highly variable and only a low proportion of published studies on RIF meet the ESHRE RIF diagnostic threshold.</p><p><strong>What is known already: </strong>RIF is a key cause of ART failure and growing focus of ART research. However, RIF remains poorly and inconsistently defined in published literature, thereby making the interpretation and clinical applicability of RIF research difficult and highly problematic.</p><p><strong>Study design size duration: </strong>The electronic databases EMBASE (Ovid), PubMed, Cochrane Central Register Of Controlled Trials (CENTRAL), Scopus, and Web of Science were systematically searched up to 30 June 2024 using the search terms 'recurrent implantation failure' and 'repeated implantation failure' for original peer-reviewed journal articles that included RIF patients.</p><p><strong>Participants/materials setting methods: </strong>The following data were manually extracted from eligible full-text articles: study methodology and characteristics, ART characteristics, and the RIF definition used. Extracted RIF definitions were analysed according to predetermined specifiers. The prognostic profile of these RIF definitions was compared with the 2023 ESHRE-recommended threshold for RIF diagnosis.</p><p><strong>Main results and the role of chance: </strong>The literature search identified 9853 studies, of which 748 were eligible for inclusion. Of these 748 studies, 589 studies (78.7%) provided one RIF definition, 83 studies (11.1%) used two definitions, three studies (0.4%) provided three or more definitions while 73 studies (9.8%) did not provide a definition for RIF. Of the 838 RIF definitions retrieved, there were a total of 503 unique RIF definitions. The three most common specifiers used to define RIF were embryo morphological quality (n = 491, 58.6% of RIF definitions), number of transfer events (n = 439, 52.4%), and cumulative number of embryos transferred (n = 326, 38.9%). RIF was most frequently diagnosed as 'failure of ≥3 embryo transfer events' (n = 26) and 'failure of ≥3 stimulated cycles' (n = 22). The threshold for defining RIF based on the cumulative number of embryos transferred in total was significantly higher for cleavage-stage embryos compared to blastocysts (incidence rate ratio 2.15, <i>P</i> < 0.001). In most cases, the RIF definitions used did not meet the ESHRE-recommended RIF diagnostic threshold of >60% cumulative predicted chance of implantation.</p><p><strong>Limitations reasons for caution: </strong>This systematic review excluded abstracts and case-series. Several studies provided RIF definitions with limited detail or ambiguous terminology with potential for misclassification or misint","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf033"},"PeriodicalIF":11.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why does the recurrent implantation failure literature need to be rewritten?","authors":"Baris Ata","doi":"10.1093/hropen/hoaf035","DOIUrl":"10.1093/hropen/hoaf035","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf035"},"PeriodicalIF":11.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between trace metal element concentrations in human blood plasma and early MAR embryological outcomes: a couple-based prospective cohort study.","authors":"Yawen Cao, Shuangshuang Bao, Qianhui Yang, Yaning Sun, Yanlan Tang, Wei Ju, Junjun Liu, Wenbin Fang, Xuemei Wang, Caiyun Wu, Chaojie Li, Peng Zhu, Shanshan Shao, Fangbiao Tao, Guixia Pan","doi":"10.1093/hropen/hoaf034","DOIUrl":"10.1093/hropen/hoaf034","url":null,"abstract":"<p><strong>Study question: </strong>What are the effects of plasma trace metal element exposure on early embryological outcomes of IVF in couples?</p><p><strong>Summary answer: </strong>Exposure to plasma trace metal elements before treatment is associated with early embryological outcomes of IVF in couples and both partners, with both harmful and beneficial effects on embryonic development.</p><p><strong>What is known already: </strong>Trace metal element exposure is one of the strongest determinants of IVF outcomes, but existing studies have certain limitations, such as the limited range of trace metal elements considered, and most have focused only on maternal exposure, overlooking the contribution of paternal exposure. Few studies have explored the association between trace metal elements and early embryological outcomes of IVF from the couples' perspective.</p><p><strong>Study design size duration: </strong>This couple-based prospective cohort study included a total of 1071 couples who underwent 1369 IVF treatment cycles between December 2020 and August 2023.</p><p><strong>Participants/materials setting methods: </strong>Plasma concentrations of 21 trace metal elements were measured by an inductively coupled plasma mass spectrometer. Early IVF embryological outcomes included two-pronuclear (2PN) zygote numbers, best-quality embryo numbers, fertilization rates, and blastocyst numbers. Elastic net regression was employed to identify trace metal elements associated with early IVF embryological outcomes in both partners and couples. K-medoids clustering was used to identify the exposure patterns of trace metal elements in couples and both partners. Joint effects of trace metal mixtures were evaluated using quantile-based g-computation (QGC) and group-weighted quantile sum (groupWQS), while independent effects of individual trace metal element were assessed using the generalized linear mixed model.</p><p><strong>Main results and the role of chance: </strong>In our study, the mean (SD) age was 32.60 (5.22) years for females and 33.79 (5.89) for males. The detection rates for all elements, except for beryllium (Be), exceeded 90%. High exposure to trace metal element mixtures in couples and male partners was associated with decreased numbers of best-quality embryos and blastocysts. Using QGC and groupWQS, we identified both harmful and beneficial metal mixtures that influence successful embryo development. Additionally, specific plasma trace metals such as iron (Fe), lithium (Li), strontium (Sr), and molybdenum (Mo) were positively associated with embryological outcomes, while metals like silver (Ag) and thallium (Tl) had adverse effects.</p><p><strong>Limitations reasons for caution: </strong>We were limited by assessing plasma trace metal elements at a single time point, focusing only on fresh embryo transfer cycles, and being unable to control for unmeasured confounding factors (e.g. psychological factors and self-reported health conditions). Mor","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf034"},"PeriodicalIF":11.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Birth defects reporting and the use of dydrogesterone: a disproportionality analysis from the World Health Organization pharmacovigilance database (VigiBase).","authors":"","doi":"10.1093/hropen/hoaf029","DOIUrl":"https://doi.org/10.1093/hropen/hoaf029","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/hropen/hoae072.].</p>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 2","pages":"hoaf029"},"PeriodicalIF":8.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12132097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Uterine smooth muscle tumours with uncertain malignant potential: reproductive and clinical outcomes in patients undergoing fertility-sparing management.","authors":"","doi":"10.1093/hropen/hoaf032","DOIUrl":"https://doi.org/10.1093/hropen/hoaf032","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/hropen/hoaf009.].</p>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 2","pages":"hoaf032"},"PeriodicalIF":8.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12132096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why does the latest pharmacovigilance data not reflect clinical experience with dydrogesterone?","authors":"Emre Pabuccu, Angela Aguilar, Roberto de Azevedo Antunes, Eran Gefen, Lee P Shulman","doi":"10.1093/hropen/hoaf030","DOIUrl":"10.1093/hropen/hoaf030","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf030"},"PeriodicalIF":8.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply: Fetal safety of dydrogesterone: clarifying the role of pharmacovigilance.","authors":"Laurent Chouchana, Alexandra Henry, Mathilde Bourdon, Chloé Maignien, Charles Chapron, Jean-Marc Treluyer, Jean Guibourdenche, Pietro Santulli","doi":"10.1093/hropen/hoaf031","DOIUrl":"10.1093/hropen/hoaf031","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf031"},"PeriodicalIF":8.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progressively diminished estrogen signaling concordant with increased fibrosis in ectopic endometrium.","authors":"Jichan Nie, Yunhua Yi, Xishi Liu, Sun-Wei Guo","doi":"10.1093/hropen/hoaf028","DOIUrl":"10.1093/hropen/hoaf028","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Do all ectopic endometrial lesions (endometriosis and adenomyosis) universally have activated estrogen signaling?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Estrogen signaling diminishes concordantly with increased fibrosis in ectopic endometrium, with deep endometriotic (DE) lesions exhibiting an estrogen biosynthesis capability and estrogen receptor β (ERβ) expression level comparable to that of control endometrium but having suppressed ERα.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Endometriosis and adenomyosis are both estrogen-dependent diseases driven by estrogen-mediated lesional development, progression, and symptom manifestation. Of note, ectopic endometrium is thought to have the ability to synthesize estradiol (E&lt;sub&gt;2&lt;/sub&gt;) &lt;i&gt;in situ&lt;/i&gt; from cholesterol due to upregulation of aromatase (CYP19A1), steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase type 2 (HSD3β2), and HSD17β1. In addition to increased estrogen biosynthesis, ERβ and G-protein coupled ER (GPER) are also overexpressed in ectopic endometrium. In particular, the prevailing view holds that prostaglandin E2 plays a vital role in facilitating estrogen biosynthesis and the upregulation of ERβ, positioning itself in the central nexus in a feed-forward loop linking hyperestrogenism and inflammation in all ectopic endometria.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;After obtaining written informed consent, we collected lesional tissues from 19 patients with ovarian endometriosis (OE) and 20 patients each with adenomyosis (AD) and DE. As controls, normal endometrial tissue samples (CT) were procured from 20 cycling women free of endometriosis and adenomyosis, and age- and menstrual phase-matched with patients in the other groups. Additionally, primary ectopic or control endometrial stromal cells derived from eight subjects in each of the OE, AD, DE, and CT groups were cultured for experiments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;We performed immunohistochemistry and western blotting to assess the expression of proteins key to the estrogen biosynthesis (StAR, HSD3β2, aromatase, and HSD17β1) and estrogen receptors (ERα, ERβ, and GPER). Fibrosis was quantified via Masson trichrome staining. Real-time RT-PCR was performed to assess corresponding gene expression levels. The estrogen concentrations in cell cultures of primary stromal cells derived from different tissues were also measured by ELISA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Among all ectopic endometrial tissue samples, the extent of lesional fibrosis was the highest in the DE lesions, followed by the AD and then the OE lesions. The protein and gene expression levels of StAR, HSD3β2, aromatase, and HSD17β1, the four proteins critically involved in estrogen biosynthesis, were significantly higher than in the CT group in OE and AD lesions, but were lowest in DE lesions, which were comparable to that of c","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf028"},"PeriodicalIF":8.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia exposure impairs male fertility via inhibiting Septin2-mediated spermatogonial proliferation.","authors":"Zhibin Li, Shuying Li, Yufeng Xiao, Junfeng Guo, Jianchun Zhou, Yang Chen, Juan Yang, Chunli Gong, Bing He, Yuyun Wu, Nannan Gao, Huan Yang, Limin Gao, Hua Hu, Yunfang Zhang, Shiming Yang","doi":"10.1093/hropen/hoaf027","DOIUrl":"10.1093/hropen/hoaf027","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;What are the molecular mechanisms underlying hypoxia-induced male reproductive impairment?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Hypoxia compromises Septin2 (&lt;i&gt;Sept2&lt;/i&gt;) transcription in spermatogonia, which impedes spermatogonial proliferation through protein phosphatase 2A (PP2A)-dependent AKT dephosphorylation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Hypoxia is associated with impaired spermatogenesis and poor sperm parameters in men. Spermatogonia proliferation, a crucial early step in spermatogenesis, is essential for maintaining the spermatogenic cell population and ensuring sperm quality. However, the connection between hypoxia and spermatogonial proliferation remains poorly understood, and treatment options for hypoxia-related reproductive disorders are limited.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;A cross-sectional study analyzed semen samples from 24 high-altitude (HA) residents, 6 pathological hypoxia (PH) patients, and 19 healthy controls to evaluate hypoxia-associated sperm parameter alterations. Complementary animal studies employing a hypobaric chamber-induced hypoxic mouse model (n = 5) confirmed reproductive impairments through assessment of birth rates, sperm quality, and testicular histopathology. Transcriptomic profiling of hypoxic versus normoxic mouse testes (n = 3/group) identified spermatogonial proliferation defects as a predominant pathological feature and pinpointed &lt;i&gt;Sept2&lt;/i&gt; as a candidate mediator. Subsequent mechanistic investigations employed &lt;i&gt;in vitro&lt;/i&gt; hypoxic culture of spermatogonial cell lines under hypoxic conditions coupled with pharmacological modulation of PP2A activity in mice (n = 3-5 per intervention group) to delineate the underlying molecular pathways.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Semen parameters were evaluated using computer-assisted sperm analysis (CASA; for sperm concentration, count, and motility), morphological staining (Pap staining for sperm deformity), and eosin-nigrosin staining (for sperm viability). In the hypoxic mouse model, fertility outcomes were assessed through fertility assessment (mating experiments), sperm parameters (CASA), testicular histology (H&E staining), and spermatogonia proliferation (immunohistochemistry and qPCR). In hypoxic spermatogonial cell models, cell proliferation was detected using CCK-8, EdU incorporation, flow cytometry, and western blotting. &lt;i&gt;Sept2&lt;/i&gt; manipulation (knockdown/overexpression), followed by mechanistic analyses (dual-luciferase reporter assay, DNA pulldown/mass spectrometry, TMT-based quantitative proteomics, co-immunoprecipitation, etc.), was performed to investigate the mechanism underlying hypoxia-regulated spermatogonia proliferation. The SEPT2 inhibitor forchlorfenuron (FCF), the PP2A agonists celastrol, erlotinib, and FTY720, as well as PP2A inhibitor okadaic acid (OA) were used to investigate the role of the SEPT2-PP2A-AKT axis in male fer","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf027"},"PeriodicalIF":8.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}