Sirine Souali-Crespo, Diana Condrea, Nadège Vernet, Betty Féret, Muriel Klopfenstein, Erwan Grandgirard, Violaine Alunni, Marie Cerciat, Matthieu Jung, Chloé Mayere, Serge Nef, Manuel Mark, Frédéric Chalmel, Norbert B Ghyselinck
To investigate the role of the nuclear receptor NR5A1 in testis after sex determination, we have analyzed mice lacking NR5A1 in Sertoli cells (SC) from embryonic day (E) 13.5 onwards. Ablation of Nr5a1 impairs the expression of genes characteristic of the SC identity (e.g., Sox9, Amh), causes SC death from E14.5 through a Trp53-independent mechanism related to anoikis, and induces disorganization of the testis cords. Together, these effects cause germ cells to enter meiosis and die. Single-cell RNA-sequencing experiments revealed that NR5A1-deficient SC change their molecular identity: some acquire a "pre-granulosa-like" identity, while other revert to a "supporting progenitor-like" cell identity, most of them being "intersex" because they express both testicular and ovarian genes...
December 8, 2023: Development