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Submitted on July 7, 2006
Accepted on February 28, 2007
Physiologie Comparée et Endocrinologie Moléculaire (LXRs, oxysterols and steroidogenic tissues), and Research Center for Human Nutrition, UMR CNRS 6547, 63177 Aubière Cedex, France; Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université Louis Pasteur, 67400 Illkirch, France; CHU Clermont-Ferrand, Service d'Anatomie Pathologique, Hôtel Dieu, 63058 Clermont-Ferrand, France; Laboratoire de Biologie du Développement et de la Reproduction, EA 975 Université d'Auvergne, 63001 Clermont-Ferrand, France; INSERM U407, Faculté de Médecine Lyon-Sud, 69921 Oullins Cedex, France
* To whom correspondence should be addressed. E-mail: j-marc.lobaccaro{at}univ-bpclermont.fr.
Oxysterol nuclear receptors Liver X receptor (LXR) 
and LXR
are known to regulate lipid homeostasis in cells exposed to high amount of cholesterol and/or fatty acids. In order to elucidate the specific and redundant roles of the LXRs in the testis, we explored the reproductive phenotypes of the mice deficient of LXR, LXR and both, of which only the lxr;-/- mice are infertile by 5 months of age. We here demonstrate that LXR-deficient mice had lower levels of testicular testosterone that correlated with a higher apoptotic rate of the germ cells. LXR-deficient mice showed increased lipid accumulation in the Sertoli cells and a lower proliferation rate of the germ cells. While, in lxr;-/- mice, fatty acid metabolism was affected through a decrease of srebp1c and increase in scd1 mRNA expression. Retinoid acid signaling pathway was also altered in lxr;-/- mice, with a higher accumulation of RAR, RAR and RALDH-2 mRNA. Combination of these alterations might explain the deleterious phenotype of infertility observed only in lxr;-/- mice, eventhough lipid homeostasis seemed to be first altered. Besides, wild-type mice treated with a specific LXR agonist showed an increase of testosterone production involving both LXR isoforms. Altogether, these data identify new roles of each LXR, collaborating to maintain both integrity and functions of the testis.
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