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  4. Bile acid-FXR alpha pathways regulate male sexual maturation in mice
 
research article

Bile acid-FXR alpha pathways regulate male sexual maturation in mice

Baptissart, Marine
•
Martinot, Emmanuelle
•
Vega, Aurelie
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2016
Oncotarget

The bile acid receptor Farnesol-X-Receptor alpha (FRX alpha) is a member of the nuclear receptor superfamily. FRX alpha is expressed in the interstitial compartment of the adult testes, which contain the Leydig cells. In adult, short term treatment (12 hours) with FRX alpha agonist inhibits the expression of steroidogenic genes via the induction of the Small heterodimer partner (SHP). However the consequences of FRX alpha 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-FRX alpha signaling is through lowering the Leydig cell sensitivity to the hypothalamo-pituitary axis, the main regulator of testicular endocrine function. In conclusion, BA-FRX alpha signaling is a critical actor during sexual maturation.

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Type
research article
DOI
10.18632/oncotarget.7153
Web of Science ID

WOS:000375804000030

Author(s)
Baptissart, Marine
Martinot, Emmanuelle
Vega, Aurelie
Sedes, Lauriane
Rouaisnel, Betty
De Haze, Angelique
Baron, Silvere
Schoonjans, Kristina  
Caira, Francoise
Volle, David H.
Date Issued

2016

Publisher

Impact Journals Llc

Published in
Oncotarget
Volume

7

Issue

15

Start page

19468

End page

19482

Subjects

testicular steroidogenesis

•

nuclear receptors

•

hypothalamo-pituitary axis

•

bile acid

•

germ cell apoptosis

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPSCHOONJANS  
Available on Infoscience
July 19, 2016
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/127255
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