Bile Acid Alters Male Mouse Fertility in Metabolic Syndrome Context

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 (TGR...

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Published in:PloS one 2015-10, Vol.10 (10), p.e0139946-e0139946
Main Authors: Vega, Aurélie, Martinot, Emmanuelle, Baptissart, Marine, De Haze, Angélique, Vaz, Frederic, Kulik, Wim, Damon-Soubeyrand, Christelle, Baron, Silvère, Caira, Françoise, Volle, David H
Format: Article
Language:English
Subjects:
Abnormalities
Acids
Animals
Apoptosis
Bile
Bile acids
Bile Acids and Salts - pharmacology
Blood-Testis Barrier - drug effects
Blood-Testis Barrier - metabolism
Body weight
Cell proliferation
Cell Proliferation - drug effects
Deoxycholic acid
Diabetes mellitus
Diabetes therapy
Diet, High-Fat
Endocrinology and metabolism
Epithelium
Farnesol
Fertility
Fertility - drug effects
G protein-coupled receptors
Glucose
High fat diet
Human health and pathology
Hépatology and Gastroenterology
Immunity
Infertility
Infertility, Male - chemically induced
Infertility, Male - metabolism
Life Sciences
Liver - metabolism
Male
Medical treatment
Metabolic syndrome
Metabolic Syndrome - complications
Metabolic Syndrome - metabolism
Mice
Molecular modelling
Nutrition
Obesity
Overweight
Overweight - complications
Overweight - metabolism
Physiology
Receptors
Reproductive Biology
Rodents
Signal Transduction
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0139946