PT  - JOURNAL ARTICLE
AU  - Okiko Habara
AU  - Catriona Y. Logan
AU  - Masami Kanai-Azuma
AU  - Roeland Nusse
AU  - Hinako M. Takase
TI  - Self-activation of Wnt signaling in pre-granulosa cells is required for ovarian folliculogenesis
AID  - 10.1101/2020.10.20.346304
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.10.20.346304
4099  - http://biorxiv.org/content/early/2020/10/21/2020.10.20.346304.short
4100  - http://biorxiv.org/content/early/2020/10/21/2020.10.20.346304.full
AB  - In mammalian ovaries, immature oocytes are reserved in primordial follicles. Precise control of primordial follicle activation (PFA) is a prerequisite for proper reproduction. Although Wnt signaling is thought to be involved in folliculogenesis, the timing and function of Wnt activity remain unclear. Here we show that canonical Wnt signaling is pivotal for the differentiation of pre-granulosa cells (pre-GCs) and subsequent oocyte maturation during PFA. We identified several Wnt ligands expressed in pre-GCs that cell-autonomously function via canonical Wnt activity. Inhibition of Wnt ligand secretion from pre-GCs/GCs led to infertility due to impaired pre-GC differentiation, whereas constitutive stabilization of β-catenin induced thickening of the pre-GCs. Our data support a two-step model of PFA in which self-activation of Wnt signaling promotes the transition of pre-GCs to GCs, and mature GCs then support oocyte reawakening. We anticipate that application of Wnt inhibitors or activators in vitro will lead to improved fertility treatments.Competing Interest StatementThe authors have declared no competing interest.