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Retinoid X receptor beta (RXRB) expression in Sertoli cells controls cholesterol homeostasis and spermiation

¹ Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Inserm U596, CNRS UMR7104, Illkirch F-67400, France² Université Louis Pasteur, Strasbourg F-67000, France³ Department of Neurobiology, Jules Stein Eye Institute, University of California, Los Angeles 90095-7002, California, USA

Correspondence should be addressed to M Mark or N B Ghyselinck at IGBMC, 1 rue Laurent Fries, BP 10142, F-67404 Illkirch Cedex, CU de Strasbourg, France; Email: manuel.mark{at}igbmc.fr; Email: norbert.ghyselinck{at}igbmc.fr

Somatic, targeted inactivation of the retinoid X receptor beta gene (Rxrb) in Sertoli cells (SC; yielding Rxrb^Ser–/– mutants) leads to failure of spermatid release, accumulation of cholesterol esters and, subsequently, testis degeneration. These abnormalities are identical, in their nature and kinetics, to those observed upon inactivating Rxrb in the whole organism, thereby demonstrating that all reproductive functions of RXRB are carried out in SC. The Rxrb^Ser–/– testis degeneration is a consequence of a cholesterol ester cell overload occurring in SC in response to reduced ABCA1- and SCARB1-mediated cholesterol efflux. The failure of spermiation was also reported in mice lacking the retinoic acid (RA) receptor- (RARA) in SC (Rara^Ser–/– mutants) and represents, in addition, a feature of vitamin A deficiency that can be readily induced in mice lacking the lecithin:retinol acyltransferase (Lrat^–/– mutants). Altogether, these findings support the conclusion that RXRB heterodimerized with a RA-liganded RARA transduces signals required in SC for spermatid release.