期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.684398
关键词
chromium (VI); spermatogonial stem cells; mitophagy; melatonin; RNA m(6)A modification
资金
- National Natural Science Foundation of China [81703193, 32002178, 31772605]
- Natural Science Foundation of Shaanxi Province, China [2019JQ-643]
- Undergraduate Training Program for Innovation and Entrepreneurship [S202010712699]
- Northwest AF University [2452019001]
Chromium (Cr) (VI) is a known toxin, mutagen, and carcinogen that can have detrimental effects on male fertility. However, melatonin pre-treatment can mitigate the toxic effects of Cr (VI) by restoring RNA m(6)A modification and activating mitochondrial fusion proteins. This study provides novel insights into the molecular mechanisms underlying the gene regulatory network responsible for mitochondrial dynamic balance and lays new experimental groundwork for treating Cr (VI)-induced damage to male fertility.
Spermatogonial stem cells (SSCs) are the basis of spermatogenesis, and any damage to SSCs may result in spermatogenic disorder and male infertility. Chromium (Cr) (VI) is a proven toxin, mutagen, and carcinogen, perpetually detrimental to environmental organisms due to its intricate and enduring detoxification process in vivo. Despite this, the deleterious effects of Cr (VI) on SSCs and the underlying mechanisms remain poorly understood. In this study, we identified that Cr (VI) impaired male reproductive system in mouse testes and induced mitochondrial dynamic imbalance and mitophagy in SSCs/progenitors. Cr (VI) also downregulated the RNA N-6-methyladenosine (m(6)A) modification levels in mitochondrial dynamic balance and mitophagy genes in SSCs/progenitors. Inspiringly, the toxic effects of Cr (VI) could be relieved by melatonin pretreatment. Melatonin alleviated Cr (VI)-induced damage to male reproductive system and autophagy in mouse testes. Melatonin also attenuated Cr (VI)-induced cell viability loss and reactive oxygen species (ROS) generation, as well as mitochondrial dynamic disorders and mitophagy in SSCs/progenitors. The protective roles of melatonin against Cr (VI)-induced mitophagy were exerted by restoration of METTL3-mediated RNA m(6)A modification and activation of mitochondrial fusion proteins MFN2 and OPA1, as well as inhibition of the mitophagy BNIP3/NIX receptor pathway. Thus, our study provides novel insights into the molecular mechanisms for RNA m(6)A modification underlying the gene regulatory network responsible for mitochondrial dynamic balance, and also lays new experimental groundwork for treatment of Cr (VI)-induced damage to male fertility.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据