Sestrin2 and Sestrin3 protect spermatogenesis against heat-induced meiotic defects

Heat stress induces testicular oxidative stress, impairs spermatogenesis, and increases the risk of male infertility. Recent studies have highlighted the antioxidative properties of the Sestrins family in reducing cellular oxidative damage. However, the role of Sestrins (Sestrin1, 2, and 3) in the t...

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Published in:Biology of reproduction 2024-07, Vol.111 (1), p.197-211
Main Authors: Chen, Wenhui, Wang, Mengchen, Wang, Huan, Jiang, Yuqing, Zhu, Jing, Zeng, Xinxin, Xie, Huihui, Yang, Qingling, Sun, Yingpu
Format: Article
Language:English
Subjects:
Apoptosis
CRISPR
DNA damage
DNA repair
Germ cells
Heat stress
Infertility
Meiosis
meiotic defects
Oxidative stress
RESEARCH ARTICLE
Sestrin
Spermatocytes
Spermatogenesis
Temperature effects
Testes
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Summary:Heat stress induces testicular oxidative stress, impairs spermatogenesis, and increases the risk of male infertility. Recent studies have highlighted the antioxidative properties of the Sestrins family in reducing cellular oxidative damage. However, the role of Sestrins (Sestrin1, 2, and 3) in the testicular response to heat stress remains unclear. Here, we found that Sestrin2 and 3 were highly expressed in the testis relative to Sestrin1. Then, the Sestrin2–/– and Sestrin3–/– mice were generated by CRISPR/Cas9 to investigate the role of them on spermatogenesis after heat stress. Our data showed that Sestrin2–/– and Sestrin3–/– mice testes exhibited more severe damage manifested by exacerbated loss of germ cells and higher levels of oxidative stress as compared to wild-type counterparts after heat stress. Notably, Sestrin2–/– and Sestrin3–/– mice underwent a remarkable increase in heat-induced spermatocyte apoptosis than that of controls. Furthermore, the transcriptome landscape of spermatocytes and chromosome spreading showed that loss of Sestrin2 and Sestrin3 exacerbated meiotic failure by compromising DNA double-strand breaks repair after heat stress. Taken together, our work demonstrated a critical protective function of Sestrin2 and Sestrin3 in mitigating the impairments of spermatogenesis against heat stress. Summary Sentence Sestrin2 and Sestrin3 play an important role in safeguarding spermatogenesis against heat-induced meiotic defects, highlighting their importance in preserving male fertility after heat stress. Graphical Abstract
ISSN:0006-3363
1529-7268
1529-7268
DOI:10.1093/biolre/ioae042