Single-Cell Transcriptomic Analysis of the Potential Mechanisms of Follicular Development in Stra8-Deficient Mice

Follicle development is a critical process in mammalian reproduction, with significant implications for ovarian reserve and fertility. <i>Stra8</i> is a known key factor regulating the initiation of meiosis; however, oocyte-like cells still appear in <i>Stra8</i>-deficient mice. Nevertheless, the underlying mechanism remains unclear and requires further investigation. Therefore, we used single-cell RNA sequencing to construct a comprehensive transcriptional atlas of ovarian cells from both wild-type and <i>Stra8</i>-deficient mice at embryonic stages E14.5 and E16.5. With stringent quality control, we obtained a total of 14,755 single cells of six major cell types. A further fine-scale analysis of the germ cell clusters revealed notable heterogeneity between wild-type and <i>Stra8</i>-deficient mice. Compared to the wild-type mice, the deficiency in <i>Stra8</i> led to the downregulation of meiosis-related genes (e.g., <i>Pigp, Tex12</i>, and <i>Sycp3</i>), and the upregulation of apoptosis-related genes (e.g., <i>Fos</i>, <i>Jun</i>, and <i>Actb</i>), thereby hindering the meiotic process. Notably, we observed that, following <i>Stra8</i> deficiency, the expression levels of <i>Sub1</i> and <i>Stk31</i> remained elevated at this stage. Furthermore, an RNA interference analysis confirmed the potential role of these genes as regulatory factors in the formation of primordial follicle-like cells. Additionally, <i>Stra8</i> deficiency disrupted the signaling between germ cells and pregranulosa cells that is mediated by Mdk-Sdc1, leading to the abnormal expression of the PI3K/AKT signaling pathway. Together, these results shed light on the molecular processes governing germ cell differentiation and folliculogenesis, emphasizing the complex role of <i>Stra8</i> in ovarian function.