Oncotarget

Research Papers:

Bile acid-FXRα pathways regulate male sexual maturation in mice

Marine Baptissart, Emmanuelle Martinot, Aurélie Vega, Lauriane Sédes, Betty Rouaisnel, Angélique de Haze, Silvère Baron, Kristina Schoonjans, Françoise Caira and David H. Volle _

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Oncotarget. 2016; 7:19468-19482. https://doi.org/10.18632/oncotarget.7153

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Abstract

Marine Baptissart1,2,3,4,*, Emmanuelle Martinot1,2,3,4,*, Aurélie Vega1,2,3,4, Lauriane Sédes1,2,3,4, Betty Rouaisnel1,2,3,4, Angélique de Haze1,2,3,4, Silvère Baron1,2,3,4, Kristina Schoonjans5, Françoise Caira1,2,3,4, David H. Volle1,2,3,4

1INSERM U 1103, Laboratoire GReD, Campus Universitaire des Cézeaux, TSA 60026, CS 60026, 63178 Aubière Cedex, France

2Université Clermont Auvergne, Université Blaise Pascal, GReD, F-63178 Aubière, France

3CNRS, UMR 6293, GReD, F-63178 Aubière, France

4Centre de Recherche en Nutrition Humaine d’Auvergne, F-63000 Clermont-Ferrand, France

5Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland

*These authors have contributed equally to this work

Correspondence to:

David H. Volle, e-mail: [email protected]

Keywords: testicular steroidogenesis, nuclear receptors, hypothalamo-pituitary axis, bile acid, germ cell apoptosis

Received: June 03, 2015    Accepted: January 22, 2016    Published: February 03, 2016

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.


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