Single-cell sequencing reveals transcriptional dynamics regulated by ERα in mouse ovaries

Context: Estrogen receptor alpha (ER alpha) 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 ER alpha-regulated transcriptional dynamics in ovarian cells using ER alpha knockout (alpha ERKO) 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 alpha ERKO mice. Bioinformatics analyses identified distinct cell populations and their transcriptional profiles post ER alpha deletion. Key Results: Distinct oocyte and granulosa cell populations were identified, with ER alpha deletion disrupting the regulation of genes linked to ovarian infertility, the ovulation cycle, and steroidogenesis. Greb1 expression in granulosa cells was found to be ER alpha-dependent. Conclusions: ER alpha 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 ER alpha's role in the reproductive system, offering insights that may lead to novel treatments for ovarian disorders.