精子发生
精子活力
精子
男科
表观遗传学
医学
生物
内科学
内分泌学
后代
遗传学
怀孕
基因
作者
Weike Shaoyong,Wusu Wang,Bo Pan,Rui Liu,Lin Yin,Reshouyang Wangjie,Haolun Tian,Yizhen Wang,Mingliang Jin
出处
期刊:ACS Nano
[American Chemical Society]
日期:2024-07-26
卷期号:18 (31): 20541-20555
标识
DOI:10.1021/acsnano.4c05660
摘要
The widespread use of colloidal copper oxide nanoparticles (CuONPs) poses substantial health risks to humans. CuONPs can penetrate the blood-testis barrier and induce spermatocide, and the understanding of the adverse effects of asthenospermia on spermatogenesis, embryonic development, and transgenerational inheritance is limited. In this study, male mice were orally administered different doses of CuONPs via continuous exposure for one spermatozoon development period (35 days) and then exposed without CuONPs for another 35 days. The CuONPs that accumulated in the testes induced oxidative stress (OS), affected the progress of spermatogenesis and sperm capacitation, and compromised epigenetic modifications, resulting in asthenospermia and embryonic development anomalies in male offspring. In a mechanism, CuONP exposure impaired the self-renewal and differentiation of spermatogonial stem cells (SSCs) via the GDNF/PI3K/AKT signaling pathway under OS. Importantly, CuONP exposure was found to potentially lower H3K9me3 levels in paternal sperm, which would further transgenerational transmission and interfere with sperm mitochondrial energy metabolism and motility, leading to asthenospermia and subfertility in the offspring. Collectively, these data reveal a molecular mechanism by which CuONP exposure disturbs H3K9me3 levels via the OS pathway, which further mediates the asthenospermic effects of reproductive failure by interfering with mitochondrial arrangement and formation in the next generation.
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