| Autor: |
Xiaoyu Wei, Zhonghao Zhang, Yayun Gu, Rong Zhang, Jie Huang, Feng Li, Yuanlin He, Shuai Lu, Yifei Wu, Wentao Zeng, Xiaorui Liu, Chenzi Liu, Jinyi Liu, Lin Ao, Fuquan Shi, Qing Chen, Yuan Lin, Jiangbo Du, Guangfu Jin, Yankai Xia, Hongxia Ma, Yuxin Zheng, Ran Huo, Jia Cao, Hongbing Shen, Zhibin Hu |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Cell Discovery, Vol 10, Iss 1, Pp 1-16 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2056-5968 |
| DOI: |
10.1038/s41421-024-00657-0 |
| Popis: |
Abstract Exposure to PM2.5, 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 PM2.5 on the reproductive health of male offspring. We have observed that paternal exposure to real-world PM2.5 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 PM2.5 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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