Liver X receptors and epididymal epithelium physiology.
OBJECTIVE
To investigate the roles of liver X receptors (LXR) in the lipid composition and gene expression regulation in the murine caput epididymidis. LXR are nuclear receptors for oxysterols, molecules derived from cholesterol metabolism that are present in mammals as two isoforms: LXRalpha, which is more specifically expressed in lipid-metabolising tissues, such as liver, adipose and steroidogenic tissues, and macrophages, whereas LXRbeta is ubiquitous. Their importance in reproductive physiology has been sustained by the fact that male mice in which the function of both LXR has been disrupted have fertility disturbances starting at the age of 5 months, leading to complete sterility by the age of 9 months. These defects are associated with epididymal epithelial degeneration in caput segments one and two, and with a sperm midpiece fragility, leading to the presence of isolated sperm heads and flagella when luminal contents are recovered from the cauda epididymidis.


METHODS
The lipid composition of the caput epididymidis of wild-type and LXR-deficient mice was assessed using oil red O staining on tissue cryosections and lipid extraction followed by high performance liquid chromatography or gas chromatography. Gene expression was checked by quantitative real time polymerase chain reaction.


RESULTS
Using LXR-deficient mice, we showed an alteration of the lipid composition of the caput epididymidis as well as a significantly decreased expression of the genes encoding SREBP1c, SCD1 and SCD2, involved in fatty acid metabolism.


CONCLUSIONS
Altogether, these results show that LXR are important regulators of epididymal function, and play a critical role in the lipid maturation processes occurring during sperm epididymal maturation.
Saez
Fabrice
F
Laboratoire Epididyme et Maturation des Gamètes, Centre de Recherche en Nutrition Humaine d'Auvergne, Université Blaise-Pascal, UMR CNRS 6547, Aubière Cedex, France. fabrice.saez@univ-bpclermont.fr
Chabory
Eléonore
E
Cadet
Rémi
R
Vernet
Patrick
P
Baron
Silvère
S
Lobaccaro
Jean-Marc A
JM
Drevet
Joël R
JR
D000818:Animals; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004822:Epididymis / Q000166:cytology / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism; D006706:Homeostasis; D008055:Lipids / Q000502:physiology; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D057093:Orphan Nuclear Receptors; D016133:Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D005227:Fatty Acids; D008055:Lipids; D000071518:Liver X Receptors; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear