Liver X receptors (LXRs) regulate lipid metabolism in the mouse epididymis

被引：0

作者：

Saez F. ^{[1
,5
]}

Ouvrier A. ^{[1
]}

Laillet B. ^{[2
]}

Cadet R. ^{[1
]}

Vernetz P. ^{[1
]}

Sion B. ^{[3
]}

Lobaccaro J.-M.A. ^{[2
,4
]}

Drevet J.R. ^{[1
]}

机构：

[1] Laboratoire Epididyme et Maturation des Gamètes, Université Biaise Pascal, CNRS UMR 6547 GEEM, 63177 Aubière Cedex

[2] UMR 1019 INRA, Université d'Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand

[3] Laboratoire de Biologie du Développement et de la Reproduction, EA 975, Faculté de Médecine, 63000 Clermont-Ferrand, Place Henri Dunant

[4] Laboratoire de Physiologie Comparée et d'Endocrinologie Moléculaire, Université Biaise Pascal, CNRS UMR 6547

[5] Université Blaise-Pascal, UMR CNRS 6547, Equipe Epididyme et Maturation des Gamètes, 63177 Aubière Cedex

来源：

Andrologie | 2007年 / 17卷 / 3期

关键词：

Cholesterol; Epididymis; Gene expression; Lipids; LXR; Nuclear receptors;

D O I：

10.1007/BF03040729

中图分类号：

学科分类号：

摘要：

This study investigated the role of Liver X Receptors (LXRs) in the lipid composition and gene expression regulation in mouse caput epididymidis. LXRs are nuclear receptors for oxysterols, molecules derived from cholesterol metabolism, which are present in mammals in two isoforms: LXRa, which is more specifically expressed in lipid metabolising tissues such as liver, adipose and steroidogenic tissues, while LXRß is ubiquitous. Their importance in reproductive physiology has been sustained by the fact that male knockout mice for both LXRs have impaired fertility from the age of 5 months, leading to complete sterility by the age of 9 months. These disorders are associated with epididymal epithelium degeneration in caput epididymidis segments one and two, and with sperm midpiece fragility, leading to the presence of isolated heads and flagellae when spermatozoa are recovered from the cauda epididymidis. To further the phenotypic characterization of LXR knockout mice, the lipid composition of caput epididymides from wild-type and LXR knockout mice was assessed using oil red O staining on tissue cryosections, lipid extraction followed by high performance liquid chromatography or gas chromatography. Gene expression was determined by quantitative real-time PCR. We showed an accumulation of cholesteryl esters in caput epididymides from Ixrβ-/- and Ixrα;β-/- mice. This accumulation was not associated with modifications in the fatty acid profiles, which are similar in all four genotypes. Changes in the expression levels of several genes are discussed in this physiological context, but cellular cholesterol efflux pathways appear to be altered in an LXRβ-dependent fashion. Altogether, these results show that LXRs are important regulators of epididymal functions, and could therefore play a key role in lipid maturation processes occurring during sperm epididymal maturation.

引用

页码：201 / 211

页数：10

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