Decoding the transcriptome of pre-granulosa cells during the formation of primordial follicles in the mouse†

Primordial follicles, a finite reservoir of eggs in mammalian ovaries, are composed of a single oocyte and its supporting somatic cells, termed granulosa cells. Although their formation may require reciprocal interplay between oocytes and pre-granulosa cells, precursors of granulosa cells, little is known about the underlying mechanisms. We addressed this issue by decoding the transcriptome of pre-granulosa cells during the formation of primordial follicles. We found that marked gene expression changes, including extracellular matrix, cell adhesion, and several signaling pathways, occur along with primordial follicle formation. Importantly, differentiation of Lgr5-EGFP-positive pre-granulosa cells to FOXL2-positive granulosa cells was delayed in mutant ovaries of the germ cell-specific genes Nanos3 and Figla, accompanied by perturbed gene expression in mutant pre-granulosa cells. These results suggest that proper development of oocytes is required for the differentiation of pre-granulosa cells. Our data provide a valuable resource for understanding the gene regulatory networks involved in the formation of primordial follicles.