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RXR beta expression in Sertoli cells controls cholesterol homeostasis and spermiation

N Vernet, Cell Biology and Development, IGBMC, Illkirch Cedex, France
C Dennefeld, Cell Biology and Development, IGBMC, Illkirch Cedex, France
M Klopfenstein, Cell Biology and Development, IGBMC, Illkirch Cedex, France
A Ruiz, Department of Neurobiology, Jules Stein Eye Institute, Los Angeles, United States
D Bok, Department of Neurobiology, Jules Stein Eye Institute, Los Angeles, United States
N Ghyselinck, Cell Biology and Development, IGBMC, Illkirch Cedex, France
M Mark, Cell Biology and Development, IGBMC, Illkirch Cedex, France

Correspondence: Norbert Ghyselinck, Email: norbert{at}igbmc.u-strasbg.fr

Abstract

Somatic, targeted, inactivation of Rxrb in Sertoli cells (yielding RxrbSer-/- mutants) leads to failure of spermatid release, accumulation of cholesterol esters and, subsequently, testis degeneration. These abnormalities are identical, in their nature and kinetic, to those observed upon inactivating Rxrb in the whole organism, thereby demonstrating that all reproductive functions of RXRbeta are carried out in Sertoli cells. The RxrbSer-/- testis degeneration is a consequence of a cholesterol ester cell overload occurring in Sertoli cells 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 alpha in Sertoli cells (RaraSer-/- mutants) and represents, in addition, a feature of vitamin A deficiency that can be readily induced in mice lacking the lecithin:retinol acyl transferase (Lrat-/- mutants). Altogether, these findings support the conclusion that RXRbeta heterodimerized with a RA-liganded RARalpha transduces signals required in Sertoli cells for spermatid release.