Progesterone receptor (PGR)-mediated transcriptional networks in human ovulatory follicles: Identification of SOX9 as a novel PGR-downstream mediator [RNA-seq]

By comparing these findings with the existing data from PgrKO mouse models, we also identified both conserved and species-specific PGR-regulated genes. Notably, SOX9 was identified as a human-specific, hCG-induced PGR-target gene in hGLCs. A further characterization study using dominant follicle samples collected before and at different times after ovulatory hCG administration from regularly cycling women demonstrated that SOX9 expression is predominantly induced in the granulosa cells of ovulatory follicles and persists in the developing corpus luteum.

Functional studies showed that SOX9 knockdown by siRNA reduced progesterone production and the expression of steroidogenesis-related genes (CYP11A1 and STAR) in hGLCs. In summary, the present finding provides the first comprehensive list of preovulatory PGR-downstream genes in human granulosa cells and unveils SOX9 as a novel human-specific ovulatory transcription factor with potential roles in steroidogenesis. This foundational information not only enhances our understanding of the PGR-regulated ovulatory pathway but also provides a critical resource for developing improved strategies to manage women’s fertility.