期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 501, 期 2, 页码 478-485出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2018.05.017
关键词
Bisphenol A (BPA); Leydig cells (LCs); miR-146a-5p; Mta3; Steroidogenesis
资金
- National Natural Science Foundation of China [31671198]
The epigenetic effects on expression of non-coding RNAs (e.g. microRNAs) of environmental toxin bisphenol A (BPA) have extended our understanding of the etiology of human reproductive disorders including hypospermatogenesis and androgen deficiency. BPA-induced miR-146a-5p is a potent regulator of endocrine and immune homeostasis, but its role in testis remain unexplored. We show here that in murine testis, miR-146a-5p was exclusively expressed in interstitial Leydig cells (LCs). This expression was significantly induced by BPA exposure. Consequently, the elevated miR-146a-5p exacerbated the deleterious effects of BPA on testicular steroidogenesis. Mechanistically, miR-146a-5p repressed the expression of Mta3, a pivotal chromatin remodeling transcription factor recently involved in controlling the steroidogenic activity, via directly targeting its 3'UTR. This repression thereafter rendered LCs more sensitive to BPA-elicited inhibitory effects. Conversely, ectopic expression of hMTA3 successfully rescued miR-146a-5p-elicited inhibitory effects on testicular steroidogenesis in BPA-challenged LCs. Taken together, the available data provide novel evidence that deregulation of testicular miR-146a-5p/Mta3 cascade mediates, at least in part, the steroidogenic dysfunction caused by BPA exposure. (C) 2018 Elsevier Inc. All rights reserved.
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