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

Abstract

Somatic, targeted inactivation of the retinoid X receptor beta gene (Rxrb) in Sertoli cells (SC; yieldingRxrbSer−/−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 inactivatingRxrbin the whole organism, thereby demonstrating that all reproductive functions of RXRB are carried out in SC. TheRxrbSer−/−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-α (RARA) in SC (RaraSer−/−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.