title: Liver X receptors interfere with the deleterious effect of diethylstilbestrol on testicular physiology.
abstract: Liver X receptors LXRα (NR1H3) and LXRβ (NR1H2) are transcription factors belonging to the nuclear receptor superfamily, activated by specific oxysterols, oxidized derivatives of cholesterol. These receptors are involved in the regulation of testis physiology. Lxr-deficient mice pointed to the physiological roles of these nuclear receptors in steroid synthesis, lipid homeostasis and germ cell apoptosis and proliferation. Diethylstilbestrol (DES) is a synthetic estrogen considered as an endocrine disruptor that affects the functions of the testis. Various lines of evidences have made a clear link between estrogens, their nuclear receptors ERα (NR3A1) and ERβ (NR3A2), and Lxrα/β. As LXR activity could also be regulated by the nuclear receptor small heterodimer partner (SHP, NR0A2) and DES could act through SHP, we wondered whether LXR could be targeted by estrogen-like endocrine disruptors such as DES. For that purpose, wild-type and Lxr-deficient mice were daily treated with 0.75 μg DES from days 1 to 5 after birth. The effects of DES were investigated at 10 or 45 days of age. We demonstrated that DES induced a decrease of the body mass at 10 days only in the Lxr-deficient mice suggesting a protective effect of Lxr. We defined three categories of DES-target genes in testis: those whose accumulation is independent of Lxr; those whose accumulation is enhanced by the lack of both Lxrα/β; those whose accumulation is repressed by the absence of Lxrα/β. Lipid accumulation is also modified by neonatal DES injection. Lxr-deficient mice present different lipid profiles, demonstrating that DES could have its effects in part due to Lxrα/β. Altogether, our study shows that both nuclear receptors Lxrα and Lxrβ are not only basally important for testicular physiology but could also have a preventive effect against estrogen-like endocrine disruptors.
authors: Clermont Université, Université Blaise Pascal, Génétique Reproduction et Développement, BP 10448, F-63000 Clermont-Ferrand, France; CNRS, UMR 6293, GReD, F-63171 Aubiere, France; INSERM, UMR 1103, GReD, F-63171 Aubiere, France; Centre de Recherche en Nutrition Humaine d'Auvergne, F-63000 Clermont-Ferrand, France; Laboratoire de Neuroendocrinologie Appliquée, Université Badji Mokhtar Annaba, BP12, 23000 Annaba, Algeria.
authors: Abdelkader
authors: A
authors: Oumeddour
authors: Clermont Université, Université Blaise Pascal, Génétique Reproduction et Développement, BP 10448, F-63000 Clermont-Ferrand, France; CNRS, UMR 6293, GReD, F-63171 Aubiere, France; INSERM, UMR 1103, GReD, F-63171 Aubiere, France; Centre de Recherche en Nutrition Humaine d'Auvergne, F-63000 Clermont-Ferrand, France.
authors: Emilie
authors: E
authors: Viennois
authors: Clermont Université, Université Blaise Pascal, Génétique Reproduction et Développement, BP 10448, F-63000 Clermont-Ferrand, France; CNRS, UMR 6293, GReD, F-63171 Aubiere, France; INSERM, UMR 1103, GReD, F-63171 Aubiere, France; Centre de Recherche en Nutrition Humaine d'Auvergne, F-63000 Clermont-Ferrand, France.
authors: Françoise
authors: F
authors: Caira
authors: Clermont Université, Université Blaise Pascal, Génétique Reproduction et Développement, BP 10448, F-63000 Clermont-Ferrand, France; CNRS, UMR 6293, GReD, F-63171 Aubiere, France; INSERM, UMR 1103, GReD, F-63171 Aubiere, France; Centre de Recherche en Nutrition Humaine d'Auvergne, F-63000 Clermont-Ferrand, France.
authors: Clélia
authors: C
authors: Decourbey
authors: Clermont Université, Université Blaise Pascal, Génétique Reproduction et Développement, BP 10448, F-63000 Clermont-Ferrand, France; CNRS, UMR 6293, GReD, F-63171 Aubiere, France; INSERM, UMR 1103, GReD, F-63171 Aubiere, France; Centre de Recherche en Nutrition Humaine d'Auvergne, F-63000 Clermont-Ferrand, France; Service d'endocrinologie, diabétologie et maladies métaboliques, CHU Clermont-Ferrand, F-63003 Clermont-Ferrand, France.
authors: Salwan
authors: S
authors: Maqdasy
authors: Laboratoire de Neuroendocrinologie Appliquée, Université Badji Mokhtar Annaba, BP12, 23000 Annaba, Algeria.
authors: Abdelkrim
authors: A
authors: Tahraoui
authors: Clermont Université, Université Blaise Pascal, Génétique Reproduction et Développement, BP 10448, F-63000 Clermont-Ferrand, France; CNRS, UMR 6293, GReD, F-63171 Aubiere, France; INSERM, UMR 1103, GReD, F-63171 Aubiere, France; Centre de Recherche en Nutrition Humaine d'Auvergne, F-63000 Clermont-Ferrand, France.
authors: Silvère
authors: S
authors: Baron
authors: Clermont Université, Université Blaise Pascal, Génétique Reproduction et Développement, BP 10448, F-63000 Clermont-Ferrand, France; CNRS, UMR 6293, GReD, F-63171 Aubiere, France; INSERM, UMR 1103, GReD, F-63171 Aubiere, France; Centre de Recherche en Nutrition Humaine d'Auvergne, F-63000 Clermont-Ferrand, France. Electronic address: david.volle@inserm.fr.
authors: David H
authors: DH
authors: Volle
authors: Clermont Université, Université Blaise Pascal, Génétique Reproduction et Développement, BP 10448, F-63000 Clermont-Ferrand, France; CNRS, UMR 6293, GReD, F-63171 Aubiere, France; INSERM, UMR 1103, GReD, F-63171 Aubiere, France; Centre de Recherche en Nutrition Humaine d'Auvergne, F-63000 Clermont-Ferrand, France. Electronic address: j-marc.lobaccaro@univ-bpclermont.fr.
authors: Jean-Marc A
authors: JM
authors: Lobaccaro
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001835:Body Weight / Q000187:drug effects; D004054:Diethylstilbestrol / Q000378:metabolism / Q000633:toxicity*; D007985:Leydig Cells / Q000187:drug effects / Q000473:pathology; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D057093:Orphan Nuclear Receptors / Q000235:genetics* / Q000378:metabolism; D012708:Sertoli Cells / Q000187:drug effects / Q000473:pathology; D013737:Testis / Q000187:drug effects* / Q000473:pathology
chemical_list: D000071518:Liver X Receptors; C000605211:Nr1h2 protein, mouse; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D004054:Diethylstilbestrol
keywords: Diethylstilbestrol; Germ cells; LXR; Nuclear receptors; Testis