SRSF1 regulates primordial follicle formation and number determination during meiotic prophase I

Serine/arginine-rich splicing factor 1 (SRSF1; previously SF2/ASF) is a pivotal posttranscriptional regulator of gene expression in various biological processes. However, the physiological roles and mechanism of SRSF1 in mouse early-stage oocytes remain elusive. Here we show that SRSF1 is essential for primordial follicle formation and number determination during meiotic prophase I. The conditional knockout of Srsf1 in mouse oocytes impairs primordial follicle formation and leads to primary ovarian insufficiency (POI). Oocyte-specific genes (e.g., LHX8, NOBOX, SOHLH1, SOHLH2, FIGLA, KIT, JAGGED1, and RAC1) that regulate primordial follicle formation are suppressed in newborn Stra8-GFPCre Srsf1Fl/Fl (cKO) mouse ovaries. However, meiotic defects are the leading cause of abnormal primordial follicle formation. In cKO mouse ovaries, immunofluorescence results suggest that the failure of synapsis and the inability to undergo recombination result in fewer homologous DNA crossovers (COs). Moreover, SRSF1 directly binds and regulates the expression of the POI-related genes Six6os1 and Msh5 via alternative splicing to implement the meiotic prophase I program. Altogether, our data reveal a critical role of the SRSF1-mediated posttranscriptional regulatory mechanism in the mouse oocyte meiotic prophase I program, which provides a framework to elucidate molecular mechanisms of the posttranscriptional network underlying primordial follicle formation. 3 WT ovary samples and 3 SRSF1-cKO ovary samples富含丝氨酸/精氨酸剪接因子1（Serine/arginine-rich splicing factor 1，SRSF1，旧称SF2/ASF）是多种生物学过程中基因表达的关键转录后调控因子。然而，SRSF1在小鼠早期卵母细胞中的生理作用及调控机制仍不明确。本研究证实，SRSF1对减数分裂I前期的原始卵泡形成与数量决定至关重要。在小鼠卵母细胞中条件性敲除Srsf1会破坏原始卵泡形成，并引发原发性卵巢功能不全（primary ovarian insufficiency，POI）。在新生Stra8-GFPCre Srsf1Fl/Fl（条件性敲除，cKO）小鼠卵巢中，调控原始卵泡形成的卵母细胞特异性基因（如LHX8、NOBOX、SOHLH1、SOHLH2、FIGLA、KIT、JAGGED1及RAC1）的表达受到抑制。然而，减数分裂缺陷是异常原始卵泡形成的首要诱因。在条件性敲除小鼠卵巢中，免疫荧光实验结果显示，同源染色体联会失败与重组受阻会导致同源DNA交叉互换（crossovers，COs）数量减少。此外，SRSF1可通过可变剪接直接结合并调控原发性卵巢功能不全相关基因Six6os1与Msh5的表达，以执行减数分裂I前期程序。综上，本研究数据揭示了SRSF1介导的转录后调控机制在小鼠卵母细胞减数分裂I前期程序中的关键作用，为阐明原始卵泡形成背后的转录后调控网络的分子机制提供了研究框架。本数据集包含3份野生型（wild type，WT）卵巢样本与3份SRSF1条件性敲除卵巢样本。