Rspo1 dependent WNT signaling safeguards ovarian development by suppressing androgen signaling
Year: 2026
Type: preprint
Abstract: Embryonic ovarian development requires high levels of WNT/ß-catenin signaling yet the molecular basis of this requirement remains unclear. Mutations in the WNT potentiator RSPO1 impair ovarian development in both mouse and human, leading to gonadal masculinization in XX individuals. Here, we show that RSPO1 acts within a restricted developmental window at the onset of ovarian differentiation and that its absence triggers precocious androgen signaling in the developing ovaries. Moreover, androgen receptor inhibition rescues ovarian development in Rspo1 mutant mice. Our findings identify RSPO1/WNT/ß-catenin signaling as an essential pathway that suppresses androgen signaling to ensure proper ovarian development in mouse.
Institutions: Centre National de la Recherche Scientifique, Inserm, Université Côte d'Azur, Institut de Biologie Valrose, École des Hautes Études en Santé Publique, Institut de Recherche en Santé, Environnement et Travail, Université de Rennes, University Hospital Carl Gustav Carus, Technische Universität Dresden, Phénotypage et ingénierie précliniques des systèmes d’organismes modèles, CELPHEDIA, Université de Strasbourg
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7214115010