Wang Han, Liu Qingchun, Cheng Shunfeng, Li Lan, Shen Wei, Ge Wei
College of Life Sciences, Key Laboratory of Animal Reproduction and Biotechnology in Universities of Shandong, Qingdao Agricultural University, Qingdao 266109, China.
Int J Mol Sci. 2025 Apr 15;26(8):3734. doi: 10.3390/ijms26083734.
Follicle development is a critical process in mammalian reproduction, with significant implications for ovarian reserve and fertility. is a known key factor regulating the initiation of meiosis; however, oocyte-like cells still appear in -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 -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 -deficient mice. Compared to the wild-type mice, the deficiency in led to the downregulation of meiosis-related genes (e.g., , and ), and the upregulation of apoptosis-related genes (e.g., , , and ), thereby hindering the meiotic process. Notably, we observed that, following deficiency, the expression levels of and 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, 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 in ovarian function.
卵泡发育是哺乳动物生殖中的一个关键过程，对卵巢储备和生育能力具有重要影响。已知是调节减数分裂起始的关键因素；然而，在基因缺陷的小鼠中仍会出现卵母细胞样细胞。尽管如此，其潜在机制仍不清楚，需要进一步研究。因此，我们使用单细胞RNA测序构建了野生型和基因缺陷型小鼠在胚胎期E14.5和E16.5时卵巢细胞的综合转录图谱。通过严格的质量控制，我们共获得了六种主要细胞类型的14,755个单细胞。对生殖细胞簇的进一步精细分析揭示了野生型和基因缺陷型小鼠之间存在显著的异质性。与野生型小鼠相比，基因缺陷导致减数分裂相关基因（如、和）下调，凋亡相关基因（如、和）上调，从而阻碍了减数分裂过程。值得注意的是，我们观察到，在基因缺陷后，此阶段和的表达水平仍保持升高。此外，RNA干扰分析证实了这些基因作为调节因子在原始卵泡样细胞形成中的潜在作用。此外，基因缺陷破坏了由Mdk-Sdc1介导的生殖细胞与颗粒前体细胞之间的信号传导，导致PI3K/AKT信号通路的异常表达。总之，这些结果揭示了控制生殖细胞分化和卵泡发生的分子过程，强调了在卵巢功能中的复杂作用。
