WNT signaling in pre-granulosa cells is required for ovarian folliculogenesis and female fertility

ABSTRACT In mammalian ovaries, immature oocytes are reserved in primordial follicles until their activation for potential ovulation. Precise control of follicle (PFA) is essential reproduction, but how this achieved unclear. Here, we show that canonical wingless-type MMTV integration site family (WNT) signaling pivotal pre-granulosa cell (pre-GC) during PFA. We identified several WNT ligands expressed pre-GCs act an autocrine manner. Inhibition secretion from pre-GCs/GCs by conditional knockout (cKO) the wntless (Wls) gene led to female infertility. Wls cKO mice, GC layer thickness was greatly reduced growing follicles, which resulted impaired oocyte growth with both abnormal, sustained nuclear localization forkhead box O3 (FOXO3) and phosphorylation ribosomal protein S6 (RPS6). Constitutive stabilization ?-catenin (CTNNB1) induced morphological changes a squamous into cuboidal form, though it did not influence activation. Our results reveal plays permissive role transition GCs, step support growth.