title: Bile Acid Alters Male Mouse Fertility in Metabolic Syndrome Context.
abstract: Bile acids have recently been demonstrated as molecules with endocrine activities controlling several physiological functions such as immunity and glucose homeostases. They act mainly through two receptors, the nuclear receptor Farnesol-X-Receptor alpha (FXRα) and the G-protein coupled receptor (TGR5). These recent studies have led to the idea that molecules derived from bile acids (BAs) and targeting their receptors must be good targets for treatment of metabolic diseases such as obesity or diabetes. Thus it might be important to decipher the potential long term impact of such treatment on different physiological functions. Indeed, BAs have recently been demonstrated to alter male fertility. Here we demonstrate that in mice with overweight induced by high fat diet, BA exposure leads to increased rate of male infertility. This is associated with the altered germ cell proliferation, default of testicular endocrine function and abnormalities in cell-cell interaction within the seminiferous epithelium. Even if the identification of the exact molecular mechanisms will need more studies, the present results suggest that both FXRα and TGR5 might be involved. We believed that this work is of particular interest regarding the potential consequences on future approaches for the treatment of metabolic diseases.
authors.affiliation: INSERM U 1103, Génétique Reproduction et Développement (GReD), F-63178 Aubière, France; Université Clermont Auvergne, 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.forename: Aurélie
authors.initials: A
authors.lastname: Vega
authors.affiliation: INSERM U 1103, Génétique Reproduction et Développement (GReD), F-63178 Aubière, France; Université Clermont Auvergne, 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.forename: Emmanuelle
authors.initials: E
authors.lastname: Martinot
authors.affiliation: INSERM U 1103, Génétique Reproduction et Développement (GReD), F-63178 Aubière, France; Université Clermont Auvergne, 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.forename: Marine
authors.initials: M
authors.lastname: Baptissart
authors.affiliation: INSERM U 1103, Génétique Reproduction et Développement (GReD), F-63178 Aubière, France; Université Clermont Auvergne, 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.forename: Angélique
authors.initials: A
authors.lastname: De Haze
authors.affiliation: Academic Medical Center, University of Amsterdam, Lab. Genetic Metabolic Diseases, F0-224, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.
authors.forename: Frederic
authors.initials: F
authors.lastname: Vaz
authors.affiliation: Academic Medical Center, University of Amsterdam, Lab. Genetic Metabolic Diseases, F0-224, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Kulik
authors.affiliation: INSERM U 1103, Génétique Reproduction et Développement (GReD), F-63178 Aubière, France; Université Clermont Auvergne, 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.forename: Christelle
authors.initials: C
authors.lastname: Damon-Soubeyrand
authors.affiliation: INSERM U 1103, Génétique Reproduction et Développement (GReD), F-63178 Aubière, France; Université Clermont Auvergne, 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.forename: Silvère
authors.initials: S
authors.lastname: Baron
authors.affiliation: Université Clermont Auvergne, 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.forename: Françoise
authors.initials: F
authors.lastname: Caira
authors.affiliation: INSERM U 1103, Génétique Reproduction et Développement (GReD), F-63178 Aubière, France; Université Clermont Auvergne, 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.forename: David H
authors.initials: DH
authors.lastname: Volle
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D001814:Blood-Testis Barrier / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D059305:Diet, High-Fat; D005298:Fertility / Q000187:drug effects*; D007248:Infertility, Male / Q000139:chemically induced* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000378:metabolism*; D051379:Mice; D050177:Overweight / Q000150:complications / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D001647:Bile Acids and Salts