Elife. 2020 May 26;9:e53972. doi: 10.7554/eLife.53972.

Nainoa Richardson¹, Isabelle Gillot¹, Elodie P Gregoire¹, Sameh A Youssef^2,3, Dirk de Rooij⁴, Alain de Bruin^2,3, Marie-Cécile De Cian^#,1, Marie-Christine Chaboissier^#,1

Affiliations

¹ Université Côte d’Azur, CNRS, Inserm, iBV, Nice, France.
² Department of Pathobiology, Dutch Molecular Pathology Center, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
³ Department Pediatrics, Divisions Molecular Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
⁴ Department of Biology, Faculty of Science, Division of Developmental Biology, Reproductive Biology Group, Utrecht University, Utrecht, Netherlands.
^# Contributed equally.

Abstract

In mammals, testicular differentiation is initiated by transcription factors SRY and SOX9 in XY gonads, and ovarian differentiation involves R-spondin1 (RSPO1) mediated activation of WNT/β-catenin signaling in XX gonads. Accordingly, the absence of RSPO1/Rspo1 in XX humans and mice leads to testicular differentiation and female-to-male sex reversal in a manner that does not requireSry or Sox9 in mice. Here we show that an alternate testis-differentiating factor exists and that this factor is Sox8. Specifically, genetic ablation of Sox8 and Sox9 prevents ovarian-to-testicular reprogramming observed in XX Rspo1 loss-of-function mice. Consequently, Rspo1 Sox8 Sox9 triple mutant gonads developed as atrophied ovaries. Thus, SOX8 alone can compensate for the loss of SOX9 for Sertoli cell differentiation during female-to-male sex reversal.

PMID: 32450947
DOI: 10.7554/eLife.53972