title: Inhibitory effect of cadmium on estrogen signaling in zebrafish brain and protection by zinc.
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. Copyright © 2016 John Wiley & Sons, Ltd.
authors: Génétique, Biodiversité et Valorisation des Bioressources, Université de Monastir, Institut Supérieur de Biotechnologie de Monastir, Tunisia.
authors: Lina
authors: L
authors: Chouchene
authors: Neuroendocrine Effects of Endocrine Disruptors, University of Rennes 1, Campus de Beaulieu, France.
authors: Elisabeth
authors: E
authors: Pellegrini
authors: Neuroendocrine Effects of Endocrine Disruptors, University of Rennes 1, Campus de Beaulieu, France.
authors: Marie-Madeleine
authors: MM
authors: Gueguen
authors: Unité d'Ecotoxicologie in vitro et in vivo, Direction des Risques Chroniques, Institut National de l'Environnement Industriel et des Risques (INERIS), Verneuil-en-Halatte, France.
authors: Nathalie
authors: N
authors: Hinfray
authors: Unité d'Ecotoxicologie in vitro et in vivo, Direction des Risques Chroniques, Institut National de l'Environnement Industriel et des Risques (INERIS), Verneuil-en-Halatte, France.
authors: François
authors: F
authors: Brion
authors: Unité d'Ecotoxicologie in vitro et in vivo, Direction des Risques Chroniques, Institut National de l'Environnement Industriel et des Risques (INERIS), Verneuil-en-Halatte, France.
authors: Benjamin
authors: B
authors: Piccini
authors: Neuroendocrine Effects of Endocrine Disruptors, University of Rennes 1, Campus de Beaulieu, France.
authors: Olivier
authors: O
authors: Kah
authors: Génétique, Biodiversité et Valorisation des Bioressources, Université de Monastir, Institut Supérieur de Biotechnologie de Monastir, Tunisia.
authors: Khaled
authors: K
authors: Saïd
authors: Génétique, Biodiversité et Valorisation des Bioressources, Université de Monastir, Institut Supérieur de Biotechnologie de Monastir, Tunisia.
authors: Imed
authors: I
authors: Messaoudi
authors: Transcription, Environnement et Cancer, Institut de Recherche en Santé-Environnement-Travail (Irset), Inserm UMR 1085, Université de Rennes 1, France.
authors: Farzad
authors: F
authors: Pakdel
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002104:Cadmium / Q000737:chemistry / Q000633:toxicity*; D002105:Cadmium Poisoning / Q000196:embryology / Q000378:metabolism / Q000517:prevention & control* / Q000662:veterinary; D002460:Cell Line; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004965:Estrogen Antagonists / Q000737:chemistry / Q000633:toxicity; D004967:Estrogens / Q000819:agonists / Q000737:chemistry / Q000378:metabolism; D005393:Fish Diseases / Q000196:embryology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D017930:Genes, Reporter / Q000187:drug effects; D006801:Humans; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014874:Water Pollutants, Chemical / Q000037:antagonists & inhibitors / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015032:Zinc / Q000627:therapeutic use*; D015053:Zygote / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D004965:Estrogen Antagonists; D004967:Estrogens; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D014874:Water Pollutants, Chemical; D029961:Zebrafish Proteins; D002104:Cadmium; D001141:Aromatase; C440728:Cyp19a1b protein, zebrafish; D015032:Zinc
keywords: aromatase; cadmium; estradiol; estrogen receptor; zinc