a State Key Laboratory of Reproductive Medicine , Nanjing Medical University , Nanjing , China.
b Department of Reproductive Medicine , Maternal and Child Health Care Hospital of Nantong City , Nantong , China.
Cell Cycle. 2019 Apr;18(8):824-833. doi: 10.1080/15384101.2019.1593648. Epub 2019 Apr 6.
The primordial follicle pool, providing all oocytes available to a female throughout her reproductive life, is established perinatally. The formation of primordial follicle pool is regulated by precise transcriptional and post-transcriptional mechanisms. Recent studies have identified several microRNAs as post-transcriptional regulatory factors in the process of primordial follicle assembly. Here, we showed that miR-92b-3p was significantly upregulated in the stage of primordial follicle assembly in newborn mouse ovaries. Inhibiting miR-92b-3p suppressed the formation of primordial follicles, while overexpression of miR-92b-3p accelerated the processes of cyst breakdown and the following primordial follicle assembly. Accordingly, the expression of follicular development-related genes was reduced upon inhibiting of miR-92b-3p and increased under miR-92b-3p overexpression. Mechanistic studies identified TSC1 as a direct target of miR-92b-3p. miR-92b-3p could activate mTOR/Rps6 signaling through targeting and inhibiting TSC1 expression. In addition, knockdown of TSC1 showed an identical phenotype with that of miR-92b-3p overexpression in accelerating processes of cyst breakdown and primordial follicle formation. Thus, our work demonstrates that miR-92b-3p is a novel regulator of primordial follicle assembly by negatively regulating TSC1 in mTOR/Rps6 signaling.
原始卵泡池为女性在整个生殖期提供所有卵母细胞，其在围产期建立。原始卵泡池的形成受精确的转录和转录后机制调控。最近的研究已经确定了几种 microRNAs 作为原始卵泡组装过程中的转录后调节因子。在这里，我们发现在新生小鼠卵巢的原始卵泡组装阶段，miR-92b-3p 显著上调。抑制 miR-92b-3p 抑制原始卵泡的形成，而过表达 miR-92b-3p 加速囊泡破裂和随后的原始卵泡形成过程。相应地，抑制 miR-92b-3p 会降低卵泡发育相关基因的表达，而过表达 miR-92b-3p 会增加这些基因的表达。机制研究确定 TSC1 是 miR-92b-3p 的直接靶标。miR-92b-3p 可以通过靶向和抑制 TSC1 表达来激活 mTOR/Rps6 信号通路。此外，TSC1 的敲低在加速囊泡破裂和原始卵泡形成过程中表现出与 miR-92b-3p 过表达相同的表型。因此，我们的工作表明，miR-92b-3p 通过负向调控 mTOR/Rps6 信号通路中的 TSC1 ，成为原始卵泡组装的一个新的调节因子。
