ArticleHuman reproduction open2025
Hypoxia exposure impairs male fertility via inhibiting Septin2-mediated spermatogonial proliferation.
Article in Human reproduction open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- High-altitude hypoxia and male reproductive dysfunction: testicular oxygen homeostasis, microenvironmental injury and spermatogonial niche vulnerability.Frontiers in endocrinology · 2026Review
- Ex Vivo Spatiotemporal Characterization of Spermatogenesis in Mouse Testicular Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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16 authors.
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Abstract
study questionWhat are the molecular mechanisms underlying hypoxia-induced male reproductive impairment? SUMMARY ANSWER: Hypoxia compromises Septin2 ( WHAT IS KNOWN ALREADY: 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. STUDY DESIGN SIZE DURATION: 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 PARTICIPANTS/MATERIALS SETTING
methodsSemen 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. MAIN RESULTS AND THE ROLE OF CHANCE: Both human populations (HA residents and PH patients) and mouse model consistently demonstrated hypoxia-related reproductive dysfunction. Mechanistic analyses revealed that hypoxia significantly downregulated LARGE SCALE DATA: RNA-seq data are deposited in China National Center for Bioinformation (CNCB) under accession number PRJCA035733. LIMITATIONS REASONS FOR CAUTION: This study focused on the effects of hypoxia on sperm parameters. Additional factors such as alterations in reproductive hormones and sexual function may contribute to hypoxia-induced infertility and warrant further research. WIDER IMPLICATIONS OF THE
findingsThis study identifies the SEPT2-PP2A/B56γ-AKT axis as a key regulator in hypoxia-related spermatogonia proliferation impairment. PP2A inhibitors such as OA may offer a therapeutic strategy to protect male fertility under hypoxic conditions. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Natural Science Foundation of China (No. 82101688) and Natural Science Foundation of Chongqing (No. CSTB2022NSCQ-MSX0943). The authors have no conflicts of interest to declare.
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