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PMID: 17124491 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Prepubertal testis development relies on retinoic acid but not rexinoid receptors in Sertoli cells.

The EMBO journal ·Vol. 25 ·No. 24 ·2006-12-13 ·Pages 5816-25

Vernet N, Dennefeld C, Guillou F, Chambon P, Ghyselinck NB, Mark M

Abstract

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.

MeSH Terms
Aging Animals Cell Count Cell Cycle Cell Polarity Epithelium Gene Expression Male Mice Phenotype Receptors, Retinoic Acid/deficiency,metabolism Retinoic Acid Receptor alpha Retinoid X Receptor alpha/metabolism Retinoid X Receptor beta/metabolism Retinoid X Receptor gamma/metabolism Retinoid X Receptors/metabolism Seminiferous Tubules/cytology Serine/genetics Sertoli Cells/metabolism Spermatogenesis/physiology Testis/cytology,growth & development,metabolism,pathology
Chemicals
Rara protein, mouse Receptors, Retinoic Acid Retinoic Acid Receptor alpha Retinoid X Receptor alpha Retinoid X Receptor beta Retinoid X Receptor gamma Retinoid X Receptors retinoic acid receptor beta retinoic acid receptor gamma Serine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Vernet Nadège
Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U596, 1 rue Laurent Fries, Illkirch F-67404, France.
Dennefeld Christine
Guillou Florian
Chambon Pierre
Ghyselinck Norbert B
Mark Manuel
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7601447
Published
2006-12-13
Epub
2006-00-23
Pages
5816-25
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1698894
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7601447 PMC Full Text View journal details
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