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This version published online on October 6, 2005
Endocrinology, doi:10.1210/en.2005-0953
A more recent version of this article appeared on January 1, 2006
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*Compound via MeSH
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*TRANS-RETINOIC ACID

Submitted on July 27, 2005
Accepted on September 22, 2005

Retinoic acid metabolism and signalling pathways in the adult and developing mouse testis

Nadège Vernet, Christine Dennefeld, Cécile Rochette-Egly, Mustapha Oulad-Abdelghani, Pierre Chambon, Norbert B. Ghyselinck, and Manuel Mark*

Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut Clinique de la Souris (ICS), Centre National de la Recherche Scientifique (CNRS) / Institut National de la Santé et de la Recherche Médicale (INSERM) / Université Louis Pasteur de Strasbourg (ULP) /Collège de France. BP10142, 67404 Illkirch Cedex, Communauté Urbaine de Strasbourg, France

* To whom correspondence should be addressed. E-mail: marek{at}igbmc.u-strasbg.fr.

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 (LRAT), RA synthesis (BCMO1, RALDHs) and RA degradation (CYP26s), as well as those of all isotypes of receptors transducing the RA signal (RARs and RXRs). Our data indicate that in adult testis (i) CYP26 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; (ii) the compartmentalization of RA synthesis within this epithelium may modulate, through paracrine mechanisms, the coupling between spermatogonia proliferation and spermatogenesis; (iii) retinyl esters synthesized in round spermatids by LRAT may be transferred and stored in Sertoli cells, in the form of ADFP-coated lipid droplets. We also show that RAR{alpha} and RXR{beta} are confined to Sertoli cells, while RAR{gamma} is expressed in spermatogonia and RAR{beta}, RXR{alpha} and RXR{gamma} are colocalised 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 RXR{beta}/RAR{alpha} heterodimers in Sertoli cells, while 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.


Key words: male reproduction • immunohistochemistry • in situ hybridization • vitamin A • nuclear receptors • blood-testis barrier • paracrine signalling




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