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Inter- and trans-generational impacts of real-world PM2.5 exposure on male-specific primary hypogonadism.

Authors :
Wei, Xiaoyu
Zhang, Zhonghao
Gu, Yayun
Zhang, Rong
Huang, Jie
Li, Feng
He, Yuanlin
Lu, Shuai
Wu, Yifei
Zeng, Wentao
Liu, Xiaorui
Liu, Chenzi
Liu, Jinyi
Ao, Lin
Shi, Fuquan
Chen, Qing
Lin, Yuan
Du, Jiangbo
Jin, Guangfu
Xia, Yankai
Source :
Cell Discovery; 4/23/2024, Vol. 10 Issue 1, p1-16, 16p
Publication Year :
2024

Abstract

Exposure to PM<subscript>2.5</subscript>, a harmful type of air pollution, has been associated with compromised male reproductive health; however, it remains unclear whether such exposure can elicit transgenerational effects on male fertility. Here, we aim to examine the effect of paternal exposure to real-world PM<subscript>2.5</subscript> on the reproductive health of male offspring. We have observed that paternal exposure to real-world PM<subscript>2.5</subscript> can lead to transgenerational primary hypogonadism in a sex-selective manner, and we have also confirmed this phenotype by using an external model. Mechanically, we have identified small RNAs (sRNAs) that play a critical role in mediating these transgenerational effects. Specifically, miR6240 and piR016061, which are present in F0 PM sperm, regulate intergenerational transmission by targeting Lhcgr and Nsd1, respectively. We have also uncovered that piR033435 and piR006695 indirectly regulate F1 PM sperm methylation by binding to the 3′-untranslated region of Tet1 mRNA. The reduced expression of Tet1 resulted in hypermethylation of several testosterone synthesis genes, including Lhcgr and Gnas, impaired Leydig cell function and ultimately led to transgenerational primary hypogonadism. Our findings provide insights into the mechanisms underlying the transgenerational effects of paternal PM<subscript>2.5</subscript> exposure on reproductive health, highlighting the crucial role played by sRNAs in mediating these effects. The findings underscore the significance of paternal pre-conception interventions in alleviating the adverse effects of environmental pollutants on reproductive health. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20565968
Volume :
10
Issue :
1
Database :
Complementary Index
Journal :
Cell Discovery
Publication Type :
Academic Journal
Accession number :
176781209
Full Text :
https://doi.org/10.1038/s41421-024-00657-0