---
title: "RSPO1-dependent WNT/β-catenin signaling suppresses androgen signaling to safeguard ovarian develop"
id: "biorxiv-8-rspo1-dependent-wnt-signaling-safeguards-ovarian-development-by-suppressing"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-8-rspo1-dependent-wnt-signaling-safeguards-ovarian-development-by-suppressing"
content_type: "clinical_feed_article"
specialty: "Endocrinology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.22.753168v1?rss=1"
published_at: "2026-09-23T09:50:14.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# RSPO1-dependent WNT/β-catenin signaling suppresses androgen signaling to safeguard ovarian develop
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-8-rspo1-dependent-wnt-signaling-safeguards-ovarian-development-by-suppressing
- **Specialty:** [Endocrinology](https://medichelpline.com/clinical-feed/endocrinology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.22.753168v1?rss=1)
- **Published At:** 2026-09-23T09:50:14.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Embryonic ovarian development requires sustained high-level **WNT/β-catenin signaling**; the molecular basis of this requirement has been unclear. - The WNT pathway potentiator **RSPO1** is critical for normal ovarian formation in mice and humans: mutations in RSPO1 impair ovarian development and can result in gonadal masculinization in XX individuals. - The study shows that RSPO1 functions within a restricted developmental window at the onset of ovarian differentiation to maintain ovarian fate. - Loss of RSPO1 triggers precocious **androgen signaling** in the developing ovary, indicating an antagonistic relationship between RSPO1/WNT activity and androgen pathways during this stage. - Pharmacologic or genetic inhibition of the **androgen receptor** rescues ovarian development in Rspo1 mutant mice, demonstrating that excessive androgen signaling is a proximate driver of masculinization in this model. - The findings identify the **RSPO1/WNT/β-catenin axis** as an essential pathway that suppresses androgen signaling to ensure proper ovarian development in mouse. - The work is reported as a preprint (not peer-reviewed). Specific experimental details, timing, and quantitative data were not reported in the abstract and source material provided here. - Funding sources declared include Agence Nationale de la Recherche, Fondation Maladies Rares/Phenomin, Deutsche Forschungsgemeinschaft, and China Scholarship Council. The authors declared no competing interests.
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Furong Tang 1 Institut de Biologie Valrose; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Furong%2BTang%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Tang%20F&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AFurong%2BTang%2B) * [ORCID record for Furong Tang](http://orcid.org/0000-0001-7546-7500 "Open in new tab") Natividad Bellido-Carreras 1 Institut de Biologie Valrose; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Natividad%2BBellido-Carreras%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Bellido-Carreras%20N&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ANatividad%2BBellido-Carreras%2B) * [ORCID record for Natividad Bellido-Carreras](http://orcid.org/0000-0003-1207-0711 "Open in new tab") Kheira Bouzid 1 Institut de Biologie Valrose; 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* [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Marie-Christine%2BChaboissier%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Chaboissier%20M&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AMarie-Christine%2BChaboissier%2B) * [ORCID record for Marie-Christine Chaboissier](http://orcid.org/0000-0003-0934-8217 "Open in new tab") * For correspondence: marie-christine.chaboissier@univ-cotedazur.fr Aitana Perea Gomez 1 Institut de Biologie Valrose; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Aitana%2BPerea%2BGomez%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Perea%20Gomez%20A&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAitana%2BPerea%2BGomez%2B) * [Abstract](https://www.biorxiv.org/content/10.64898/2026.09.22.753168v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5802738/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.09.22.753168v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5802738/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.09.22.753168v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5802738/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.09.22.753168v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5802738/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Embryonic ovarian development requires high levels of WNT/B-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/B-catenin signaling as an essential pathway that suppresses androgen signaling to ensure proper ovarian development in mouse. ### Competing Interest Statement The authors have declared no competing interest. ## Funder Information Declared Agence Nationale de la Recherche, ANR-19-CE14-0022, ANR-23-CE14-0012 Fondation Maladies Rares, Phenomin 2013 Deutsche Forschungsgemeinschaft, INST 269/910-1 FUGG China Scholarship Council, 201506300094 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a [CC-BY-NC-ND 4.0 International license](http://creativecommons.org/licenses/by-nc-nd/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. 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