Inhibitory effect of cadmium on estrogen signaling in zebrafish brain and protection by zincReportar como inadecuado

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* Corresponding author 1 Université de Monastir 2 Irset - Institut de recherche, santé, environnement et travail Rennes 3 INERIS - Institut National de l-Environnement Industriel et des Risques

Abstract : The present study was conducted to assess the effects of Cd exposure on estrogen signaling in the zebrafish brain, as well as the potential protective role of Zn against Cd-induced toxicity. For this purpose, the effects on transcriptional activation of the estrogen receptors ERs, aromatase B Aro-B protein expression and molecular expression of related genes were examined in vivo using wild-type and transgenic zebrafish embryos. For in vitro studies, an ER-negative glial cell line U251MG transfected with different zebrafish ER subtypes ERα, ERβ1 and ERβ2 was also used. Embryos were exposed either to estradiol E2, Cd, E2+Cd or E2+Cd+Zn for 72 h and cells were exposed to the same treatments for 30 h. Our results show that E2 treatment promoted the transcriptional activation of ERs and increased Aro-B expression, at both the protein and mRNA levels. Although exposure to Cd, does not affect the studied parameters when administered alone, it significantly abolished the E2-stimulated transcriptional response of the reporter gene for the three ER subtypes in U251-MG cells, and clearly inhibited the E2 induction of Aro-B in radial glial cells of zebrafish embryos. These inhibitory effects were accompanied by a significant downregulation of the expression of esr1, esr2a, esr2b and cyp19a1b genes compared to the E2-treated group used as a positive control. Zn administration during simultaneous exposure to E2 and Cd strongly stimulated zebrafish ERs transactivation and increased Aro-B protein expression, whereas mRNA levels of the three ERs as well as the cyp19a1b remained unchanged in comparison with Cd-treated embryos. In conclusion, our results clearly demonstrate that Cd acts as a potent anti-estrogen in vivo and in vitro, and that Cd-induced E2 antagonism can be reversed, at the protein level, by Zn supplement.

Keywords : Aromatase Cadmium Estradiol estrogen receptor Zinc

Autor: Lina Chouchene - Elisabeth Pellegrini - Marie-Madeleine Gueguen - Nathalie Hinfray - François Brion - Benjamin Piccini - Olivier



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