Overexpression of MicroRNA-10a in Germ Cells Causes Male Infertility by Targeting Rad51 in Mouse and Human
Overexpression of MicroRNA-10a in Germ Cells Causes Male Infertility by Targeting Rad51 in Mouse and Human
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小鼠和人类生殖细胞中 MicroRNA-10a 的过度表达通过靶向 Rad51 导致男性不育
DOI：
10.3389/fphys.2019.00765
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发表时间：
2019-06-18
影响因子：
4
通讯作者：
Dong, Wuzi
中科院分区：
文献类型：
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作者：
Gao, Huihui;Wen, Hui;Dong, Wuzi
精子发生是一个复杂的过程，包括精原干细胞自我更新和分化为成熟精子。microRNAs（miRNAs）作为一类小分子非编码RNA，在精子发生过程中起着重要作用。然而，大量miRNAs在精子发生中的作用及其可能的机制尚不清楚。在这里，我们表明，遗传条件下过表达的miR-10a在生殖细胞引起完全的雄性不育，其特征是减数分裂阻滞在生殖细胞。对miR-10a过表达小鼠睾丸的分析表明，双链断裂（DSB）修复失败和精原细胞分化异常。此外，通过生物信息学预测和荧光素酶检测，我们确定Rad 51是miR-10a在生殖细胞中的关键靶点，可能是导致miR-10a过表达小鼠和生殖细胞停滞患者不育的原因。我们的数据表明，miR-10a依赖的减数分裂过程的遗传调控是至关重要的雄性生殖细胞发育和精子发生在小鼠和人类。这些发现有助于我们理解miRNA-10a在精子发生和男性生育力中的作用。
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.