title: Spermatogonia differentiation requires retinoic acid receptor γ.
abstract: Vitamin A is instrumental to mammalian reproduction. Its metabolite, retinoic acid (RA), acts in a hormone-like manner through binding to and activating three nuclear receptor isotypes, RA receptor (RAR)α (RARA), RARβ, and RARγ (RARG). Here, we show that 1) RARG is expressed by A aligned (A(al)) spermatogonia, as well as during the transition from A(al) to A(1) spermatogonia, which is known to require RA; and 2) ablation of Rarg, either in the whole mouse or specifically in spermatogonia, does not affect meiosis and spermiogenesis but impairs the A(al) to A(1) transition in the course of some of the seminiferous epithelium cycles. Upon ageing, this phenomenon yields seminiferous tubules containing only spermatogonia and Sertoli cells. Altogether, our findings indicate that RARG cell-autonomously transduces, in undifferentiated spermatogonia of adult testes, a RA signal critical for spermatogenesis. During the prepubertal spermatogenic wave, the loss of RARG function can however be compensated by RARA, as indicated by the normal timing of appearance of meiotic cells in Rarg-null testes. Accordingly, RARG- and RARA-selective agonists are both able to stimulate Stra8 expression in wild-type prepubertal testes. Interestingly, inactivation of Rarg does not impair expression of the spermatogonia differentiation markers Kit and Stra8, contrary to vitamin A deficiency. This latter observation supports the notion that the RA-signaling pathway previously shown to operate in Sertoli cells also participates in spermatogonia differentiation.
authors: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de Santé et de Recherche Médicale Unité 964, Centre National de Recherche Scientifique Unité Mixte de Recherche 7104, Université de Strasbourg, 67404 Illkirch, France.
authors: Aurore
authors: A
authors: Gely-Pernot
authors: Mathilde
authors: M
authors: Raverdeau
authors: Catherine
authors: C
authors: Célébi
authors: Christine
authors: C
authors: Dennefeld
authors: Betty
authors: B
authors: Feret
authors: Muriel
authors: M
authors: Klopfenstein
authors: Shosei
authors: S
authors: Yoshida
authors: Norbert B
authors: NB
authors: Ghyselinck
authors: Manuel
authors: M
authors: Mark
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008540:Meiosis; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D018168:Receptors, Retinoic Acid / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology*; D013093:Spermatogonia / Q000166:cytology* / Q000378:metabolism*; D013737:Testis / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D014802:Vitamin A Deficiency / Q000378:metabolism / Q000473:pathology; D000097768:Retinoic Acid Receptor gamma
chemical_list: D017931:DNA Primers; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D000097768:Retinoic Acid Receptor gamma; C000607072:Rara protein, mouse