LXR and ABCA1 control cholesterol homeostasis in the proximal mouse epididymis in a cell-specific manner.
Mammalian spermatozoa undergo important plasma membrane maturation steps during epididymal transit. Among these, changes in lipids and cholesterol are of particular interest as they are necessary for fertilization. However, molecular mechanisms regulating these transformations inside the epididymis are still poorly understood. Liver X receptors (LXRs), the nuclear receptors for oxysterols, are of major importance in intracellular cholesterol homeostasis, and LXR(-/-)-deficient male mice have already been shown to have reduced fertility at an age of 5 months and complete sterility for 9-month-old animals. This sterility phenotype is associated with testes and caput epididymides epithelial defects. The research presented here was aimed at investigating how LXRs act in the male caput epididymidis by analyzing key actors in cholesterol homeostasis. We show that accumulation of cholesteryl esters in LXR(-/-) male mice is associated with a specific loss of ABCA1 and an increase in apoptosis of apical cells of the proximal caput epididymidis. ATP-binding cassette G1 (ABCG1) and scavenger receptor B1 (SR-B1), two other cholesterol transporters, show little if any modifications. Our study also revealed that SR-B1 appears to have a peculiar expression pattern along the epididymal duct. These results should help in understanding the functional roles of LXR in cholesterol trafficking processes in caput epididymidis.
Ouvrier
Aurélia
A
Université Blaise Pascal, Unité Mixte de Recherche GReD Centre National de la Recherche Scientifique 6247, INSERM U931, 63177 Aubiere, cedex, France.
Cadet
Rémi
R
Vernet
Patrick
P
Laillet
Brigitte
B
Chardigny
Jean-Michel
JM
Lobaccaro
Jean-Marc A
JM
Drevet
Joël R
JR
Saez
Fabrice
F
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D001692:Biological Transport; D002784:Cholesterol / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D004822:Epididymis / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D004847:Epithelial Cells / Q000473:pathology; D005227:Fatty Acids / Q000378:metabolism; D005298:Fertility; D006706:Homeostasis; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D009928:Organ Specificity; D057093:Orphan Nuclear Receptors / Q000378:metabolism*; D013079:Sperm Maturation
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D002788:Cholesterol Esters; D005227:Fatty Acids; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D002784:Cholesterol