DEGs in granulosa cells.

Context: Estrogen receptor α (ERα) is a key regulator of reproductive function, particularly in ovarian development and function, yet the specifics of its role at the molecular level remain unclear. Aims: The study aims to elucidate the molecular mechanisms of ERα-regulated transcriptional dynamics in ovarian cells using ERα knockout (αERKO) mice created via CRISPR/Cas9. Methods: Single-cell RNA sequencing (scRNA-seq) was used to compare transcriptomes from individual ovarian cells in both wild type and αERKO mice. Bioinformatics analyses identified distinct cell populations and their transcriptional profiles post ERα deletion. Key Results: Distinct oocyte and granulosa cell populations were identified, with ERα deletion disrupting the regulation of genes linked to ovarian infertility, the ovulation cycle, and steroidogenesis. Greb1 expression in granulosa cells was found to be ERα-dependent. Conclusions: ERα deletion significantly alters the transcriptional landscape of ovarian cells, affecting genes and pathways central to ovarian function and the ovulation process. Implications: The findings provide an in-depth, single-cell view of ERα’s role in the reproductive system, offering insights that may lead to novel treatments for ovarian disorders.【背景】雌激素受体α（Estrogen receptor α, ERα）是生殖功能的关键调控因子，尤其在卵巢发育与功能维持中发挥核心作用，但其分子层面的具体调控机制仍不明确。【研究目的】本研究旨在借助CRISPR/Cas9构建的雌激素受体α敲除（αERKO）小鼠，解析卵巢细胞中ERα调控的转录动态分子机制。【研究方法】本研究采用单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）技术，对比野生型与αERKO小鼠的单个卵巢细胞转录组；通过生物信息学分析，鉴定ERα敲除后的不同细胞群及其转录谱。【主要结果】本研究鉴定出独特的卵母细胞与颗粒细胞群，ERα敲除会扰乱与卵巢不育、排卵周期及类固醇生成相关的基因调控；同时发现颗粒细胞中Greb1的表达依赖于ERα。【研究结论】ERα敲除可显著改变卵巢细胞的转录组全貌，影响卵巢功能与排卵过程核心相关的基因及通路。【研究意义】本研究为ERα在生殖系统中的作用提供了深入的单细胞视角，其研究结果可为卵巢疾病的新型治疗方案提供新思路。