Abstract
AbstractFemale fertility is dictated by the number of oocyte-containing primordial follicles within the ovary. These follicles are established early in development and their selective activation represents the definitive first step towards oocyte maturation and ovulation. The intrinsic molecular mechanisms that regulate ovarian follicle activation are largely uncharacterised. In this study, we report a single-cell RNA sequencing (scRNAseq) dataset to examine mouse embryonic and neonatal ovaries across the developmental window of primordial follicle formation and activation. We identified five distinct clusters of granulosa cells and bioinformatic analysis revealed a population of pregranulosa cells that appeared to be undergoing follicle activation. This cluster was uniquely differentiated by the expression ofTnni3, Slc18a2, Fam13aandKlf2, all of which are novel to follicle activation. Finally, we examined the transcriptome of a mouse model where all primordial follicles enter folliculogenesis simultaneously (Cdkn1b-/-) and showed that the signature genes of activating pregranulosa cells was observed precociously inCdkn1b-/-ovaries, further demonstrating that p27kip1acts as an important repressor of follicle activation. Combined, this data provides insight into how primordial follicle activation is regulated in mammals and could be utilised to identify pathways to target to improve fertility preservation and infertility conditions in the future.Graphical abstract
Publisher
Cold Spring Harbor Laboratory