ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
Chronic Hypoxia Disrupts Spermatogenesis Through ASXL2-EZH2-Mediated Microtubule Destabilization.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. 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.
- Circadian Disruption Is Associated with Elevated Whole-Semen mtDNA Copy Number and ImplicatesInternational journal of molecular sciences · 2026Article
- High-altitude hypoxia and male reproductive dysfunction: testicular oxygen homeostasis, microenvironmental injury and spermatogonial niche vulnerability.Frontiers in endocrinology · 2026Review
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Authors and funding
12 authors.
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Abstract
Chronic hypoxia disrupts spermatogenesis by blocking the round-to-elongated spermatid transition, a process governed by the additional sex combs-like 2 (ASXL2)-enhancer of zeste homolog 2 (EZH2) axis. Hypoxia downregulates ASXL2 expression, which reduces EZH2 binding to the 3482-3511 bp region of the CEP162 promoter. This impairment decreases H3K27me3 modification while increasing CEP162 transcription. Overexpressed CEP162 competes with TUBA3A for TUBB3 binding. This competition depletes ciliary TUBB3 levels, destabilizing axonemal microtubules. These structural defects are correlated with sperm malformations and functional deficiencies. In infertile men, diminished ASXL2 and EZH2 expression highlights the therapeutic potential of targeting this axis for hypoxia-related spermatogenic disorders.
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