title: Bile acid-FXRα pathways regulate male sexual maturation in mice.
abstract: The bile acid receptor Farnesol-X-Receptor alpha (FRXα) is a member of the nuclear receptor superfamily. FRXα is expressed in the interstitial compartment of the adult testes, which contain the Leydig cells. In adult, short term treatment (12 hours) with FRXα agonist inhibits the expression of steroidogenic genes via the induction of the Small heterodimer partner (SHP). However the consequences of FRXα activation on testicular pathophysiology have never been evaluated. We demonstrate here that mice fed a diet supplemented with bile acid during pubertal age show increased incidence of infertility. This is associated with altered differentiation and increase apoptosis of germ cells due to lower testosterone levels. At the molecular level, next to the repression of basal steroidogenesis via the induction expression of Shp and Dax-1, two repressors of steroidogenesis, the main action of the BA-FRXα signaling is through lowering the Leydig cell sensitivity to the hypothalamo-pituitary axis, the main regulator of testicular endocrine function. In conclusion, BA-FRXα signaling is a critical actor during sexual maturation.
authors: INSERM U 1103, Laboratoire GReD, Campus Universitaire des Cézeaux, TSA 60026, CS 60026, 63178 Aubière Cedex, France.|Université Clermont Auvergne, Université Blaise Pascal, GReD, F-63178 Aubière, France.|CNRS, UMR 6293, GReD, F-63178 Aubière, France.|Centre de Recherche en Nutrition Humaine d'Auvergne, F-63000 Clermont-Ferrand, France.
authors: Marine
authors: M
authors: Baptissart
authors: INSERM U 1103, Laboratoire GReD, Campus Universitaire des Cézeaux, TSA 60026, CS 60026, 63178 Aubière Cedex, France.|Université Clermont Auvergne, Université Blaise Pascal, GReD, F-63178 Aubière, France.|CNRS, UMR 6293, GReD, F-63178 Aubière, France.|Centre de Recherche en Nutrition Humaine d'Auvergne, F-63000 Clermont-Ferrand, France.
authors: Emmanuelle
authors: E
authors: Martinot
authors: INSERM U 1103, Laboratoire GReD, Campus Universitaire des Cézeaux, TSA 60026, CS 60026, 63178 Aubière Cedex, France.|Université Clermont Auvergne, Université Blaise Pascal, GReD, F-63178 Aubière, France.|CNRS, UMR 6293, GReD, F-63178 Aubière, France.|Centre de Recherche en Nutrition Humaine d'Auvergne, F-63000 Clermont-Ferrand, France.
authors: Aurélie
authors: A
authors: Vega
authors: INSERM U 1103, Laboratoire GReD, Campus Universitaire des Cézeaux, TSA 60026, CS 60026, 63178 Aubière Cedex, France.|Université Clermont Auvergne, Université Blaise Pascal, GReD, F-63178 Aubière, France.|CNRS, UMR 6293, GReD, F-63178 Aubière, France.|Centre de Recherche en Nutrition Humaine d'Auvergne, F-63000 Clermont-Ferrand, France.
authors: Lauriane
authors: L
authors: Sédes
authors: INSERM U 1103, Laboratoire GReD, Campus Universitaire des Cézeaux, TSA 60026, CS 60026, 63178 Aubière Cedex, France.|Université Clermont Auvergne, Université Blaise Pascal, GReD, F-63178 Aubière, France.|CNRS, UMR 6293, GReD, F-63178 Aubière, France.|Centre de Recherche en Nutrition Humaine d'Auvergne, F-63000 Clermont-Ferrand, France.
authors: Betty
authors: B
authors: Rouaisnel
authors: INSERM U 1103, Laboratoire GReD, Campus Universitaire des Cézeaux, TSA 60026, CS 60026, 63178 Aubière Cedex, France.|Université Clermont Auvergne, Université Blaise Pascal, GReD, F-63178 Aubière, France.|CNRS, UMR 6293, GReD, F-63178 Aubière, France.|Centre de Recherche en Nutrition Humaine d'Auvergne, F-63000 Clermont-Ferrand, France.
authors: Angélique
authors: A
authors: de Haze
authors: INSERM U 1103, Laboratoire GReD, Campus Universitaire des Cézeaux, TSA 60026, CS 60026, 63178 Aubière Cedex, France.|Université Clermont Auvergne, Université Blaise Pascal, GReD, F-63178 Aubière, France.|CNRS, UMR 6293, GReD, F-63178 Aubière, France.|Centre de Recherche en Nutrition Humaine d'Auvergne, F-63000 Clermont-Ferrand, France.
authors: Silvère
authors: S
authors: Baron
authors: Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
authors: Kristina
authors: K
authors: Schoonjans
authors: INSERM U 1103, Laboratoire GReD, Campus Universitaire des Cézeaux, TSA 60026, CS 60026, 63178 Aubière Cedex, France.|Université Clermont Auvergne, Université Blaise Pascal, GReD, F-63178 Aubière, France.|CNRS, UMR 6293, GReD, F-63178 Aubière, France.|Centre de Recherche en Nutrition Humaine d'Auvergne, F-63000 Clermont-Ferrand, France.
authors: Françoise
authors: F
authors: Caira
authors: INSERM U 1103, Laboratoire GReD, Campus Universitaire des Cézeaux, TSA 60026, CS 60026, 63178 Aubière Cedex, France.|Université Clermont Auvergne, Université Blaise Pascal, GReD, F-63178 Aubière, France.|CNRS, UMR 6293, GReD, F-63178 Aubière, France.|Centre de Recherche en Nutrition Humaine d'Auvergne, F-63000 Clermont-Ferrand, France.
authors: David H
authors: DH
authors: Volle
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D019826:Cholic Acid / Q000008:administration & dosage / Q000494:pharmacology; D005298:Fertility / Q000187:drug effects; D007555:Isoxazoles / Q000494:pharmacology; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D034622:RNA Interference; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D012741:Sexual Maturation / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D013737:Testis / Q000166:cytology / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D001647:Bile Acids and Salts; D019826:Cholic Acid; D007555:Isoxazoles; D018160:Receptors, Cytoplasmic and Nuclear; D013739:Testosterone; D000099150:Receptor, Farnesoid X-Activated; C412815:GW 4064
keywords: bile acid; germ cell apoptosis; hypothalamo-pituitary axis; nuclear receptors; testicular steroidogenesis