Chronic Hypoxia Disrupts Spermatogenesis Through ASXL2–EZH2–Mediated Microtubule Destabilization
Source abstract
Abstract
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.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: High Altitude and Hypoxia · Cancer, Hypoxia, and Metabolism · Sperm and Testicular Function
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Pathophysiology Army Medical University Chongqing China
Key Laboratory of Extreme Environmental Medicine Ministry of Education of China Chongqing China
Key Laboratory of High Altitude Medicine PLA Chongqing China
Department of Dermatology Southwest Hospital Army Medical University Chongqing China
National Key Laboratory of Advanced Biotechnology Academy of Military Medical Sciences Beijing Beijing China
Chongqing International Institute for Immunology Chongqing China
Department of Immunology Army Medical University Chongqing China
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