Bile Acid Alters Male Mouse Fertility in Metabolic Syndrome Context

PLoS One. 2015 Oct 6;10(10):e0139946. doi: 10.1371/journal.pone.0139946. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile Acids and Salts / pharmacology*
  • Blood-Testis Barrier / drug effects
  • Blood-Testis Barrier / metabolism
  • Cell Proliferation / drug effects
  • Diet, High-Fat
  • Fertility / drug effects*
  • Infertility, Male / chemically induced*
  • Infertility, Male / metabolism
  • Liver / metabolism
  • Male
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / metabolism*
  • Mice
  • Overweight / complications
  • Overweight / metabolism*
  • Signal Transduction

Substances

  • Bile Acids and Salts

Grant support

This work was funded by Inserm, CNRS, Clermont Université, Ministère de l’Enseignement Supérieur et de la Recherche (to MB), Ligue contre le Cancer (Comité Puy de Dôme to DHV), Nouveau Chercheur Auvergne (to SB and #R12087CC to DHV), and ANR Jeune Chercheur (#1103 to DHV). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.