title: Dietary cholesterol-induced post-testicular infertility.
abstract: This work shows that an overload of dietary cholesterol causes complete infertility in dyslipidemic male mice (the Liver X Receptor-deficient mouse model). Infertility resulted from post-testicular defects affecting the fertilizing potential of spermatozoa. Spermatozoa of cholesterol-fed lxr-/- animals were found to be dramatically less viable and motile, and highly susceptible to undergo a premature acrosome reaction. We also provide evidence, that this lipid-induced infertility is associated with the accelerated appearance of a highly regionalized epididymal phenotype in segments 1 and 2 of the caput epididymidis that was otherwise only observed in aged LXR-deficient males. The epididymal epithelial phenotype is characterized by peritubular accumulation of cholesteryl ester lipid droplets in smooth muscle cells lining the epididymal duct, leading to their transdifferentiation into foam cells that eventually migrate through the duct wall, a situation that resembles the inflammatory atherosclerotic process. These findings establish the high level of susceptibility of epididymal sperm maturation to dietary cholesterol overload and could partly explain reproductive failures encountered by young dyslipidemic men as well as ageing males wishing to reproduce.
authors.affiliation: Equipe Epididyme et Maturation des Gamètes, Clermont Université, Université Blaise Pascal, UMR GReD, Génétique Reproduction & Développement, CNRS 6247, INSERM U931, Aubière, France.
authors.forename: Aurélia
authors.initials: A
authors.lastname: Ouvrier
authors.forename: Georges
authors.initials: G
authors.lastname: Alves
authors.forename: Christelle
authors.initials: C
authors.lastname: Damon-Soubeyrand
authors.forename: Geoffroy
authors.initials: G
authors.lastname: Marceau
authors.forename: Rémi
authors.initials: R
authors.lastname: Cadet
authors.forename: Laurent
authors.initials: L
authors.lastname: Janny
authors.forename: Florence
authors.initials: F
authors.lastname: Brugnon
authors.forename: Ayhan
authors.initials: A
authors.lastname: Kocer
authors.forename: Aurélien
authors.initials: A
authors.lastname: Pommier
authors.forename: Jean-Marc A
authors.initials: JM
authors.lastname: Lobaccaro
authors.forename: Joël R
authors.initials: JR
authors.lastname: Drevet
authors.forename: Fabrice
authors.initials: F
authors.lastname: Saez
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D007248:Infertility, Male / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013737:Testis / Q000187:drug effects*
chemical_list: D002791:Cholesterol, Dietary
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