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Prepubertal testis development relies on retinoic acid but not rexinoid receptors in Sertoli cells
Author(s) -
Vernet Nadège,
Dennefeld Christine,
Guillou Florian,
Chambon Pierre,
Ghyselinck Norbert B,
Mark Manuel
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601447
Subject(s) - physics , retinoic acid , humanities , biology , philosophy , gene , genetics
Sertoli cells (SC) are instrumental to stem spermatogonia differentiation, a process that critically depends on retinoic acid (RA). We show here that selective ablation of RA receptor alpha (RARalpha) gene in mouse SC, singly ( Rara Ser−/− mutation) or in combination with RARbeta and RARgamma genes ( Rara/b/g Ser−/− mutation), abolishes cyclical gene expression in these cells. It additionally induces testis degeneration and delays spermatogonial expression of Stra8 , two hallmarks of RA deficiency. As identical defects are generated upon inactivation of RARalpha in the whole organism, our data demonstrate that all the functions exerted by RARalpha in male reproduction are Sertoli cell‐autonomous. They further indicate that RARalpha is a master regulator of the cyclical activity of SC and controls paracrine pathways required for spermatogonia differentiation and germ cell survival. Most importantly, we show that the ablation of all RXR (alpha, beta and gamma isotypes) in SC does not recapitulate the phenotype generated upon ablation of all three RARs, thereby providing the first evidence that RARs exert functions in vivo independently of RXRs.