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Mixture Concentration-Response Modeling Reveals Antagonistic Effects of Estradiol and Genistein in Combination on Brain Aromatase Gene (cyp19a1b) in Zebrafish

Comprehension of compound interactions in mixtures is of increasing interest to scientists, especially from a perspective of mixture risk assessment. However, most of conducted studies have been dedicated to the effects on gonads, while only few of them were. interested in the effects on the central...

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Autores principales: Hinfray, Nathalie, Tebby, Cleo, Piccini, Benjamin, Bourgine, Gaelle, Aït-Aïssa, Sélim, Porcher, Jean-Marc, Pakdel, Farzad, Brion, François
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979603/
https://www.ncbi.nlm.nih.gov/pubmed/29614754
http://dx.doi.org/10.3390/ijms19041047
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author Hinfray, Nathalie
Tebby, Cleo
Piccini, Benjamin
Bourgine, Gaelle
Aït-Aïssa, Sélim
Porcher, Jean-Marc
Pakdel, Farzad
Brion, François
author_facet Hinfray, Nathalie
Tebby, Cleo
Piccini, Benjamin
Bourgine, Gaelle
Aït-Aïssa, Sélim
Porcher, Jean-Marc
Pakdel, Farzad
Brion, François
author_sort Hinfray, Nathalie
collection PubMed
description Comprehension of compound interactions in mixtures is of increasing interest to scientists, especially from a perspective of mixture risk assessment. However, most of conducted studies have been dedicated to the effects on gonads, while only few of them were. interested in the effects on the central nervous system which is a known target for estrogenic compounds. In the present study, the effects of estradiol (E2), a natural estrogen, and genistein (GEN), a phyto-estrogen, on the brain ER-regulated cyp19a1b gene in radial glial cells were investigated alone and in mixtures. For that, zebrafish-specific in vitro and in vivo bioassays were used. In U251-MG transactivation assays, E2 and GEN produced antagonistic effects at low mixture concentrations. In the cyp19a1b-GFP transgenic zebrafish, this antagonism was observed at all ratios and all concentrations of mixtures, confirming the in vitro effects. In the present study, we confirm (i) that our in vitro and in vivo biological models are valuable complementary tools to assess the estrogenic potency of chemicals both alone and in mixtures; (ii) the usefulness of the ray design approach combined with the concentration-addition modeling to highlight interactions between mixture components.
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spelling pubmed-59796032018-06-10 Mixture Concentration-Response Modeling Reveals Antagonistic Effects of Estradiol and Genistein in Combination on Brain Aromatase Gene (cyp19a1b) in Zebrafish Hinfray, Nathalie Tebby, Cleo Piccini, Benjamin Bourgine, Gaelle Aït-Aïssa, Sélim Porcher, Jean-Marc Pakdel, Farzad Brion, François Int J Mol Sci Article Comprehension of compound interactions in mixtures is of increasing interest to scientists, especially from a perspective of mixture risk assessment. However, most of conducted studies have been dedicated to the effects on gonads, while only few of them were. interested in the effects on the central nervous system which is a known target for estrogenic compounds. In the present study, the effects of estradiol (E2), a natural estrogen, and genistein (GEN), a phyto-estrogen, on the brain ER-regulated cyp19a1b gene in radial glial cells were investigated alone and in mixtures. For that, zebrafish-specific in vitro and in vivo bioassays were used. In U251-MG transactivation assays, E2 and GEN produced antagonistic effects at low mixture concentrations. In the cyp19a1b-GFP transgenic zebrafish, this antagonism was observed at all ratios and all concentrations of mixtures, confirming the in vitro effects. In the present study, we confirm (i) that our in vitro and in vivo biological models are valuable complementary tools to assess the estrogenic potency of chemicals both alone and in mixtures; (ii) the usefulness of the ray design approach combined with the concentration-addition modeling to highlight interactions between mixture components. MDPI 2018-04-01 /pmc/articles/PMC5979603/ /pubmed/29614754 http://dx.doi.org/10.3390/ijms19041047 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hinfray, Nathalie
Tebby, Cleo
Piccini, Benjamin
Bourgine, Gaelle
Aït-Aïssa, Sélim
Porcher, Jean-Marc
Pakdel, Farzad
Brion, François
Mixture Concentration-Response Modeling Reveals Antagonistic Effects of Estradiol and Genistein in Combination on Brain Aromatase Gene (cyp19a1b) in Zebrafish
title Mixture Concentration-Response Modeling Reveals Antagonistic Effects of Estradiol and Genistein in Combination on Brain Aromatase Gene (cyp19a1b) in Zebrafish
title_full Mixture Concentration-Response Modeling Reveals Antagonistic Effects of Estradiol and Genistein in Combination on Brain Aromatase Gene (cyp19a1b) in Zebrafish
title_fullStr Mixture Concentration-Response Modeling Reveals Antagonistic Effects of Estradiol and Genistein in Combination on Brain Aromatase Gene (cyp19a1b) in Zebrafish
title_full_unstemmed Mixture Concentration-Response Modeling Reveals Antagonistic Effects of Estradiol and Genistein in Combination on Brain Aromatase Gene (cyp19a1b) in Zebrafish
title_short Mixture Concentration-Response Modeling Reveals Antagonistic Effects of Estradiol and Genistein in Combination on Brain Aromatase Gene (cyp19a1b) in Zebrafish
title_sort mixture concentration-response modeling reveals antagonistic effects of estradiol and genistein in combination on brain aromatase gene (cyp19a1b) in zebrafish
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979603/
https://www.ncbi.nlm.nih.gov/pubmed/29614754
http://dx.doi.org/10.3390/ijms19041047
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