Overexpression of MicroRNA-10a in Germ Cells Causes Male Infertility by Targeting Rad51 in Mouse and Human

生殖细胞中 MicroRNA-10a 的过度表达通过靶向小鼠和人类的 Rad51 导致男性不育

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作者:Huihui Gao, Hui Wen, Congcong Cao, Daqian Dong, Chenhao Yang, Shengsong Xie, Jin Zhang, Xunbin Huang, Xingxu Huang, Shuiqiao Yuan, Wuzi Dong

Abstract

Spermatogenesis is a complicated process including spermatogonial stem cells self-renewal and differentiates into mature spermatozoa. MicroRNAs (miRNAs) as a class of small non-coding RNAs play a crucial role during the process of spermatogenesis. However, the function of a plenty of miRNAs on spermatogenesis and the potential mechanisms remain largely unknown. Here, we show that genetically conditional overexpressed miR-10a in germ cells caused complete male sterility, characterized by meiotic arrested in germ cells. Analysis of miR-10a overexpression mouse testes reveals that failure of double strand break (DSB) repairs and aberrant spermatogonial differentiation. Furthermore, we identified Rad51 as a key target of miR-10a in germ cell by bioinformatics prediction and luciferase assay, which may be responsible for the infertility of the miR-10a overexpressed mice and germ cell arrested patients. Our data show that miR-10a dependent genetic regulation of meiotic process is crucial for male germ cell development and spermatogenesis in both mouse and human. These findings facilitate our understanding of the roles of miRNA-10a in spermatogenesis and male fertility.

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