生物
精子发生
代谢组学
机制(生物学)
肠道菌群
精子
微生物群
下调和上调
生理学
生殖成功
男科
免疫学
生物信息学
内分泌学
遗传学
医学
人口
哲学
认识论
基因
环境卫生
作者
Zi‐Run Jin,Yan Yang,Yalei Cao,Quan Wen,Xiaofeng Yu,Jianxing Cheng,Qiancheng Zhao,J. Weng,Kai Hong,Hui Jiang,Jing Hang,Zhe Zhang
出处
期刊:Microbiome
[Springer Nature]
日期:2023-09-27
卷期号:11 (1)
被引量:2
标识
DOI:10.1186/s40168-023-01659-y
摘要
Aging-related fertility decline is a prevalent concern globally. Male reproductive system aging is mainly characterized by a decrease in sperm quality and fertility. While it is known that intestinal physiology changes with age and that microbiota is shaped by physiology, the underlying mechanism of how the microbiota affects male reproductive aging is still largely unexplored.Here, we utilized fecal microbiota transplantation (FMT) to exchange the fecal microbiota between young and old mice. Cecal shotgun metagenomics and metabolomics were used to identify differences in gut microbiota composition and metabolic regulation during aging. Our results demonstrated that FMT from young to old mice alleviated aging-associated spermatogenic dysfunction through an unexpected mechanism mediated by a gut bacteria-derived metabolite, 3-hydroxyphenylacetic acid (3-HPAA). 3-HPAA treatment resulted in an improvement of spermatogenesis in old mice. RNA sequencing analysis, qRT-PCR and Western blot revealed that 3-HPAA induced an upregulation of GPX4, thereby restraining ferroptosis and restoring spermatogenesis. These findings were further confirmed by in vitro induction of ferroptosis and inhibition of GPX4 expression.Our results demonstrate that the microbiome-derived metabolite, 3-HPAA, facilitates spermatogenesis of old mice through a ferroptosis-mediated mechanism. Overall, these findings provide a novel mechanism of dysregulated spermatogenesis of old mice, and suggest that 3-HPAA could be a potential therapy for fertility decline of aging males in clinical practice. Video Abstract.
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