Chronic Hypoxia Disrupts Spermatogenesis Through ASXL2–EZH2–Mediated Microtubule Destabilization

Advanced Science 2026 Open access

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Authors: Jun Yin, Mengjie Zhang, Wenying Liu, Wenlong Shen, Debao Li, Hongming Miao, Fang Deng, Gang Zhang, Yi Tian, Yi Zhang (9093), Zhihu Zhao, B. Ni
DOI: 10.1002/advs.202501266
Cited by: 4
References: 61

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.

Fields of Study & Subjects

High Altitude and Hypoxia Cancer Hypoxia and Metabolism Sperm and Testicular Function

Publication details

Journal / source
Advanced Science
Publisher
Wiley
Volume
13
Issue
26
Pages
e01266–e01266
Publication date
4 March 2026
Language
EN