Puberty is a key event for the development of male reproductive functions. It depends on the increase of testosterone produced by the testis, under the control of the activity of the hypothalamic-pituitary axis. Ultimately, this leads to the maturation of secondary sexual characteristics, to the establishment and maintenance of spermatogenesis and fertility.
Impaired growth and delayed puberty can be found in case of progressive familial intrahepatic cholestasis. In this context, the levels of bile acids (BA) are greatly increased. David Volle’s team therefore hypothesized that the increase in bile acid levels could impair testicular function during puberty.
They demonstrate that mice fed a diet supplemented with bile acids during puberty show an increased incidence of male infertility. This is associated with a defect in the differentiation of germ cells by an increase in cell death resulting from lower levels of testosterone. At the molecular level, the nuclear receptor for bile acids FXRa represses the synthesis of testicular steroids via induction of the expression of SHP gene and Dax-1, two repressors of the steroid synthesis. However, the BA-FRXα signaling acts primarily by decreasing the sensitivity of Leydig cells in the hypothalamic-pituitary axis, the main regulator of the endocrine function of the testis.
These data reinforce the links between FXRα and steroid metabolism. This is even more important than endocrine homeostasis is an essential physiological process, whose alteration leads to various diseases (infertility, obesity, diabetes). This work defines FXRα well as an important player in the regulation of the physiology of the testis during puberty, especially in the control of gametogenesis. This is of interest to better understand the etiology of primary hypogonadism observed in the case of liver disorders during puberty, as demonstrated in experimental models. This also opens up new avenues of research on identifying actors or diagnostic predictions with regard to the increasing incidence of male infertility.
This work has been highlighted on the CNRS website (in French) http://www.cnrs.fr/insb/recherche/parutions/articles2016/d-volle.html
For more informations ….
Baptissart M, Martinot E, Vega A, Sédes L, Rouaisnel B, de Haze A, Baron S, Schoonjans K, Caira F, Volle DH. Bile acid-FXRα pathways regulate male sexual maturation in mice. Oncotarget. 2016 Feb 3. doi:10.18632/oncotarget.7153.
David H. Volle, e-mail: firstname.lastname@example.org