title: Liver X Receptors (LXRs) Alpha and Beta Play Distinct Roles in the Mouse Epididymis.
abstract: After its production in the testis, a spermatozoon has to undergo posttesticular maturation steps to become fully motile and fertile. The first step is epididymal maturation, during which immature spermatozoa are transformed into biochemically mature cells ready to proceed to the next step, capacitation, a physiological process occurring in the female genital tract. The biochemical transformations include modification of sperm lipid composition during epididymal transit, with significant changes in fatty acids, phospholipids, and sterols between the caput and the cauda epididymal spermatozoa. Although quantitative aspects of these changes are well documented for several mammalian species, molecular mechanisms governing these steps are poorly understood. Transgenic male mice invalidated for the two liver X receptors (LXRalpha and LXRbeta, nuclear oxysterol receptors regulating cholesterol and lipid metabolism) become sterile when aging, showing an epididymal phenotype. We used single-knockout-model mice to characterize the role of each LXR isoform during sperm maturation in the epididymis. We show here that although a certain redundancy exists in the functions of the two LXR isoforms, some physiological processes are more under the influence of only one of them. In both cases, aging males showed slight subfertility, associated with dyslipidemia, emphasizing the importance of lipid metabolism in relation with male fertility.
authors.affiliation: Equipe "Mécanismes post-testiculaires de l'infertilité," Clermont Université, Université Blaise Pascal, UMR GReD (Génétique Reproduction & Développement) CNRS 6293, INSERM U1103, Aubière, France.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Whitfield
authors.affiliation: Equipe "Mécanismes post-testiculaires de l'infertilité," Clermont Université, Université Blaise Pascal, UMR GReD (Génétique Reproduction & Développement) CNRS 6293, INSERM U1103, Aubière, France.
authors.forename: Aurélia
authors.initials: A
authors.lastname: Ouvrier
authors.affiliation: Equipe "Mécanismes post-testiculaires de l'infertilité," Clermont Université, Université Blaise Pascal, UMR GReD (Génétique Reproduction & Développement) CNRS 6293, INSERM U1103, Aubière, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Cadet
authors.affiliation: Equipe "Mécanismes post-testiculaires de l'infertilité," Clermont Université, Université Blaise Pascal, UMR GReD (Génétique Reproduction & Développement) CNRS 6293, INSERM U1103, Aubière, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Damon-Soubeyrand
authors.affiliation: Equipe "Mécanismes post-testiculaires de l'infertilité," Clermont Université, Université Blaise Pascal, UMR GReD (Génétique Reproduction & Développement) CNRS 6293, INSERM U1103, Aubière, France.
authors.forename: Rachel
authors.initials: R
authors.lastname: Guiton
authors.affiliation: Equipe "Mécanismes post-testiculaires de l'infertilité," Clermont Université, Université Blaise Pascal, UMR GReD (Génétique Reproduction & Développement) CNRS 6293, INSERM U1103, Aubière, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Janny
authors.affiliation: Equipe "Mécanismes post-testiculaires de l'infertilité," Clermont Université, Université Blaise Pascal, UMR GReD (Génétique Reproduction & Développement) CNRS 6293, INSERM U1103, Aubière, France.
authors.forename: Ayhan
authors.initials: A
authors.lastname: Kocer
authors.affiliation: "Retinoids, Reproduction Developmental Diseases," School of Medicine, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France Biochemistry and Molecular Biology Department, CHU Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: Geoffroy
authors.initials: G
authors.lastname: Marceau
authors.affiliation: Equipe "Mécanismes post-testiculaires de l'infertilité," Clermont Université, Université Blaise Pascal, UMR GReD (Génétique Reproduction & Développement) CNRS 6293, INSERM U1103, Aubière, France.
authors.forename: Hanae
authors.initials: H
authors.lastname: Pons-Rejraji
authors.affiliation: Equipe "Lipides, récepteurs nucléaires et troubles chez l'homme" & Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH), Clermont Université, Université Blaise Pascal, UMR GReD (Génétique Reproduction & Développement) CNRS 6293, INSERM U1103, Aubière, France.
authors.forename: Amalia
authors.initials: A
authors.lastname: Trousson
authors.affiliation: Equipe "Mécanismes post-testiculaires de l'infertilité," Clermont Université, Université Blaise Pascal, UMR GReD (Génétique Reproduction & Développement) CNRS 6293, INSERM U1103, Aubière, France joel.drevet@univ-bpclermont.fr.
authors.forename: Joël R
authors.initials: JR
authors.lastname: Drevet
authors.affiliation: Equipe "Mécanismes post-testiculaires de l'infertilité," Clermont Université, Université Blaise Pascal, UMR GReD (Génétique Reproduction & Développement) CNRS 6293, INSERM U1103, Aubière, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Saez
mesh_terms: D000375:Aging; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D004822:Epididymis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006706:Homeostasis; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D000071518:Liver X Receptors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D018873:Pregnancy Rate; D020033:Protein Isoforms
chemical_list: D000071518:Liver X Receptors; D020033:Protein Isoforms; D002784:Cholesterol
keywords: LXR; cholesterol homeostasis; epididymis; inflammation; lipids; spermatozoa