Retinoid X receptor beta (RXRB) expression in Sertoli cells controls cholesterol homeostasis and spermiation.
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-alpha (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.
Vernet
Nadège
N
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Inserm U596, CNRS UMR7104, Illkirch F-67400, France.
Dennefeld
Christine
C
Klopfenstein
Muriel
M
Ruiz
Alberto
A
Bok
Dean
D
Ghyselinck
Norbert B
NB
Mark
Manuel
M
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D019281:Dimerization; D015870:Gene Expression; D005786:Gene Expression Regulation; D006706:Homeostasis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D049230:Retinoid X Receptor beta / Q000235:genetics / Q000378:metabolism*; D051122:Scavenger Receptors, Class B / Q000235:genetics; D012708:Sertoli Cells / Q000378:metabolism*; D013087:Spermatids / Q000502:physiology*
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D049230:Retinoid X Receptor beta; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D002784:Cholesterol