Prepubertal testis development relies on retinoic acid but not rexinoid receptors in Sertoli cells.
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.
Vernet
Nadège
N
Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U596, 1 rue Laurent Fries, Illkirch F-67404, France.
Dennefeld
Christine
C
Guillou
Florian
F
Chambon
Pierre
P
Ghyselinck
Norbert B
NB
Mark
Manuel
M
D000375:Aging; D000818:Animals; D002452:Cell Count; D002453:Cell Cycle; D016764:Cell Polarity; D004848:Epithelium; D015870:Gene Expression; D008297:Male; D051379:Mice; D010641:Phenotype; D018168:Receptors, Retinoic Acid / Q000172:deficiency / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D047490:Retinoid X Receptor alpha / Q000378:metabolism; D049230:Retinoid X Receptor beta / Q000378:metabolism; D047491:Retinoid X Receptor gamma / Q000378:metabolism; D047488:Retinoid X Receptors / Q000378:metabolism*; D012671:Seminiferous Tubules / Q000166:cytology; D012694:Serine / Q000235:genetics; D012708:Sertoli Cells / Q000378:metabolism*; D013091:Spermatogenesis / Q000502:physiology; D013737:Testis / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism* / Q000473:pathology; D000097768:Retinoic Acid Receptor gamma
D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047490:Retinoid X Receptor alpha; D049230:Retinoid X Receptor beta; D047491:Retinoid X Receptor gamma; D047488:Retinoid X Receptors; D012694:Serine; D000097768:Retinoic Acid Receptor gamma; C000607072:Rara protein, mouse; C082925:retinoic acid receptor beta