Retinoic acid metabolism and signaling pathways in the adult and developing mouse testis.
As a first step in investigating the role of retinoic acid (RA) in mouse testis, we analyzed the distribution pattern of the enzymes involved in vitamin A storage (lecithin:retinol acyltransferase), RA synthesis (beta-carotene 15,15'-monoxygenase and retinaldehyde dehydrogenases) and RA degradation (cytochrome P450 hydroxylases) as well as those of all isotypes of receptors transducing the RA signal [RA receptors (RARs) and rexinoid receptors (RXRs)]. Our data indicate that in adult testis 1) cytochrome P450 hydroxylase enzymes may generate in peritubular myoid cells a catabolic barrier that prevents circulating RA and RA synthesized by Leydig cells to enter the seminiferous epithelium; 2) the compartmentalization of RA synthesis within this epithelium may modulate, through paracrine mechanisms, the coupling between spermatogonia proliferation and spermatogenesis; 3) retinyl esters synthesized in round spermatids by lecithin:retinol acyltransferase may be transferred and stored in Sertoli cells, in the form of adipose differentiation-related protein-coated lipid droplets. We also show that RARalpha and RXRbeta are confined to Sertoli cells, whereas RARgamma is expressed in spermatogonia and RARbeta, RXRalpha, and RXRgamma are colocalized in step 7-8 spermatids. Correlating these expression patterns with the pathological phenotypes generated in response to RAR and RXR mutations and to postnatal vitamin A deficiency suggests that spermiation requires RXRbeta/RARalpha heterodimers in Sertoli cells, whereas spermatogonia proliferation involves, independently of RXR, two distinct RAR-mediated signaling pathways in both Sertoli cells and spermatogonia. Our data also suggest that the involvement of RA in testis development starts when primary spermatogonia first appear.
Vernet
Nadège
N
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Université Louis Pasteur de Strasbourg (ULP)/Collège de France, 67404 Illkirch Cedex, Communauté Urbaine de Strasbourg, France.
Dennefeld
Christine
C
Rochette-Egly
Cécile
C
Oulad-Abdelghani
Mustapha
M
Chambon
Pierre
P
Ghyselinck
Norbert B
NB
Mark
Manuel
M
D000818:Animals; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000502:physiology; D000072482:Retinoic Acid Receptor alpha; D015398:Signal Transduction; D013737:Testis / Q000254:growth & development* / Q000502:physiology; D014212:Tretinoin / Q000378:metabolism*
C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; C082925:retinoic acid receptor beta; D014212:Tretinoin