The microRNA miR-202 prevents precocious spermatogonial differentiation and meiotic initiation during mouse spermatogenesis.

Jian Chen, Chenxu Gao, Xiwen Lin, Yan Ning, Wei He, Chunwei Zheng, Daoqin Zhang, Lin Yan, Binjie Jiang, Yuting Zhao, Md Alim Hossen, Chunsheng Han

Development (Cambridge, England) 2021 Dec 15

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Spermatogonial differentiation and meiotic initiation during spermatogenesis are tightly regulated by a number of genes, including those encoding enzymes for miRNA biogenesis. However, whether and how single miRNAs regulate these processes remain unclear. Here, we report that miR-202, a member of the let-7 family, prevents precocious spermatogonial differentiation and meiotic initiation in spermatogenesis by regulating the timely expression of many genes, including those for key regulators such as STRA8 and DMRT6. In miR-202 knockout (KO) mice, the undifferentiated spermatogonial pool is reduced, accompanied by age-dependent decline of fertility. In KO mice, SYCP3, STRA8 and DMRT6 are expressed earlier than in wild-type littermates, and Dmrt6 mRNA is a direct target of miR-202-5p. Moreover, the precocious spermatogonial differentiation and meiotic initiation were also observed in KO spermatogonial stem cells when cultured and induced in vitro, and could be partially rescued by the knockdown of Dmrt6. Therefore, we have not only shown that miR-202 is a regulator of meiotic initiation but also identified a previously unknown module in the underlying regulatory network. © 2021. Published by The Company of Biologists Ltd.

Citation

Jian Chen, Chenxu Gao, Xiwen Lin, Yan Ning, Wei He, Chunwei Zheng, Daoqin Zhang, Lin Yan, Binjie Jiang, Yuting Zhao, Md Alim Hossen, Chunsheng Han. The microRNA miR-202 prevents precocious spermatogonial differentiation and meiotic initiation during mouse spermatogenesis. Development (Cambridge, England). 2021 Dec 15;148(24)