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

Title WNT signaling in pre-granulosa cells is required for ovarian folliculogenesis and female fertility.
Publication Type Journal Article
Year of Publication 2021
Authors Habara OLogan CYKanai-Azuma MNusse RTakase HM
Journal Development (Cambridge, England)
Volume 148
Issue 9
Date Published 2021 May 1
ISSN 0950-1991
Abstract In mammalian ovaries, immature oocytes are reserved in primordial follicles until their activation for potential ovulation. Precise control of primordial follicle activation (PFA) is essential for reproduction, but how this is achieved is unclear. Here, we show that canonical wingless-type MMTV integration site family (WNT) signaling is pivotal for pre-granulosa cell (pre-GC) activation during PFA. We identified several WNT ligands expressed in pre-GCs that act in an autocrine manner. Inhibition of WNT secretion from pre-GCs/GCs by conditional knockout (cKO) of the wntless (Wls) gene led to female infertility. In Wls cKO mice, GC layer thickness was greatly reduced in growing follicles, which resulted in impaired oocyte growth with both an abnormal, sustained nuclear localization of forkhead box O3 (FOXO3) and reduced phosphorylation of ribosomal protein S6 (RPS6). Constitutive stabilization of β-catenin (CTNNB1) in pre-GCs/GCs induced morphological changes of pre-GCs from a squamous into a cuboidal form, though it did not influence oocyte activation. Our results reveal that canonical WNT signaling plays a permissive role in the transition of pre-GCs to GCs, which is an essential step to support oocyte growth.
URL https://journals.biologists.com/dev/article-lookup/doi/10.1242/dev.198846
DOI 10.1242/dev.198846
Short Title Development
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