Rspo1 dependent WNT signaling safeguards ovarian development by suppressing androgen signaling

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.

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BibTeX

@misc{tang2026rspo1,
  title = {{Rspo1 dependent WNT signaling safeguards ovarian development by suppressing androgen signaling}},
  author = {Furong Tang and Natividad Bellido-Carreras and Kheira Bouzid and Aurélie Lardenois and Thomas A Darde and Magali Dhellemmes and Aurélie Despoux and Mirko Peitzsch and Marie-Christine Birling and Frédéric Chalmel and Marie-Christine Chaboissier and Aitana Perea Gomez},
  howpublished = {HAL},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.22.753168},
  url = {https://hal.science/hal-05760574v1},
  note = {CC BY-NC-ND 4.0},
}

RIS

TY  - UNPB
TI  - Rspo1 dependent WNT signaling safeguards ovarian development by suppressing androgen signaling
AU  - Furong Tang
AU  - Natividad Bellido-Carreras
AU  - Kheira Bouzid
AU  - Aurélie Lardenois
AU  - Thomas A Darde
AU  - Magali Dhellemmes
AU  - Aurélie Despoux
AU  - Mirko Peitzsch
AU  - Marie-Christine Birling
AU  - Frédéric Chalmel
AU  - Marie-Christine Chaboissier
AU  - Aitana Perea Gomez
PY  - 2026
DA  - 2026/09/22
PB  - HAL
DO  - 10.64898/2026.09.22.753168
UR  - https://hal.science/hal-05760574v1
AB  - 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.
ER  -

Abstract

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