The microRNA miR-202 prevents precocious spermatogonial differentiation and meiotic initiation during mouse spermatogenesis
The microRNA miR-202 prevents precocious spermatogonial differentiation and meiotic initiation during mouse spermatogenesis
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microRNA miR-202 可防止小鼠精子发生过程中的早熟精原细胞分化和减数分裂起始。
DOI：
10.1242/dev.199799
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发表时间：
2021-12-01
期刊：
影响因子：
4.6
通讯作者：
Han, Chunsheng
中科院分区：
文献类型：
--
作者：
Chen, Jian;Gao, Chenxu;Han, Chunsheng
精原细胞分化和减数分裂起始在精子发生过程中受到许多基因的严格调控，包括那些编码miRNA生物合成酶的基因。然而，单个miRNAs是否以及如何调控这些过程仍不清楚。在这里，我们报告说，miR-202，let-7家族的成员，防止早熟精原细胞分化和减数分裂启动精子发生通过调节许多基因的及时表达，包括那些关键的监管机构，如STRA 8和DMRT 6。在miR-202敲除（KO）小鼠中，未分化的精原细胞池减少，伴随着生育力的年龄依赖性下降。在KO小鼠中，SYCP 3、STRA 8和DMRT 6的表达早于野生型同窝小鼠，并且Dmrt 6 mRNA是miR-202- 5 p的直接靶标。此外，KO精原干细胞在体外培养和诱导过程中也出现了精原细胞的早熟分化和减数分裂的启动，并可通过敲低Dmrt 6而得到部分挽救。因此，我们不仅证明了miR-202是减数分裂起始的调节因子，而且还在潜在的调控网络中鉴定了一个以前未知的模块。
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.