Authors: Saez, Fabrice¹; Chabory, Eléonore¹; Cadet, Rémi¹; Vernet, Patrick¹; Baron, Silvère²; Lobaccaro, Jean-Marc A.²; Drevet, Joël R.¹

Source: Asian Journal of Andrology, Volume 9, Number 4, July 2007 , pp. 574-582(9)

Publisher: Wiley-Blackwell

Abstract:

Aim: 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: LXRα, which is more specifically expressed in lipid-metabolising tissues, such as liver, adipose and steroidogenic tissues, and macrophages, whereas LXRβ 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. Conclusion: 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.

Keywords: epididymis; liver X receptors; nuclear receptors; lipids; cholesterol; gene expression

Document Type: Original article

DOI: http://dx.doi.org/10.1111/j.1745-7262.2007.00301.x

Affiliations: 1: Laboratoire Epididyme et Maturation des Gamètes, Université Blaise Pascal, CNRS UMR 6547, Aubière Cedex 63177, France 2: Laboratoire de Physiologie Cellulaire et d'Endocrinologie Moléculaire, and Centre de Recherche en Nutrition Humaine d'Auvergne, Université Blaise Pascal, CNRS UMR 6547, Aubière Cedex 63177, France

Publication date: 2007-07-01

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