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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2018
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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. |
format | Online Article Text |
id | pubmed-5979603 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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