Additive effects of levonorgestrel and ethinylestradiol on brain aromatase (cyp19a1b) in zebrafish specific in vitro and in vivo bioassays

Autor: Clémentine Garoche, G. Bourgine, François Brion, Benjamin Piccini, Nathalie Hinfray, Selim Ait-Aissa, Farzad Pakdel, Cleo Tebby, Olivier Kah
Přispěvatelé: Chard-Hutchinson, Xavier, Institut National de l'Environnement Industriel et des Risques (INERIS), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), ANR-13-CESA-0006-03, ANR, French National Research Agency, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), ANR-13-CESA-0006,PROOFS,Occurrence et effets de ligands environnementaux des récepteurs de la progestérone sur la reproduction et le neurodéveloppement du poisson(2013)
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Embryo
Nonmammalian
010501 environmental sciences
Pharmacology
Ethinyl Estradiol
Toxicology
01 natural sciences
Animals
Genetically Modified
Genes
Reporter
Bioassay
Drug Interactions
Aromatase
Luciferases
ETHINYLESTRADIOL
BRAIN AROMATASE
Zebrafish
[SDV.TOX.ECO] Life Sciences [q-bio]/Toxicology/Ecotoxicology
biology
Brain
3. Good health
Biological Assay
[SDV.TOX.ECO]Life Sciences [q-bio]/Toxicology/Ecotoxicology
medicine.drug
animal structures
Green Fluorescent Proteins
Cell Line
03 medical and health sciences
In vivo
Ethinylestradiol
medicine
U251-MG CELLS
Animals
Estrogen Receptor beta
Humans
[SDV.EE.SANT] Life Sciences [q-bio]/Ecology
environment/Health
Estrogen receptor beta
0105 earth and related environmental sciences
[SDV.EE.SANT]Life Sciences [q-bio]/Ecology
environment/Health
Reporter gene
MIXTURE
Estrogen Receptor alpha
LEVONORGESTREL
Estrogens
Zebrafish Proteins
biology.organism_classification
030104 developmental biology
TRANSGENIC ZEBRAFISH
biology.protein
Progestins
Estrogen receptor alpha
Zdroj: Toxicology and Applied Pharmacology
Toxicology and Applied Pharmacology, 2016, 307, pp.108-114. ⟨10.1016/j.taap.2016.07.023⟩
Toxicology and Applied Pharmacology, Elsevier, 2016, 307, pp.108-114. ⟨10.1016/j.taap.2016.07.023⟩
ISSN: 0041-008X
1096-0333
DOI: 10.1016/j.taap.2016.07.023
Popis: International audience; Estrogens and progestins are widely used in combination in human medicine and both are present in aquatic environment. Despite the joint exposure of aquatic wildlife to estrogens and progestins, very little information is available on their combined effects. In the present study we investigated the effect of ethinylestradiol (EE2) and Levonorgestrel (LNG), alone and in mixtures, on the expression of the brain specific ER-regulated cyp19a1b gene. For that purpose, recently established zebrafish-derived tools were used: (i) an in vitro transient reporter gene assay in a human glial cell line (U251-MG) co-transfected with zebrafish estrogen receptors (zfERs) and the luciferase gene under the control of the zebrafish cyp19a1b gene promoter and (ii) an in vivo bioassay using a transgenic zebrafish expressing GFP under the control of the zebrafish cyp19a1b gene promoter (cyp19a1b-GFP). Concentration-response relationships for single chemicals were modeled and used to design the mixture experiments following a ray design. The results from mixture experiments were analyzed to predict joint effects according to concentration addition and statistical approaches were used to characterize the potential interactions between the components of the mixtures (synergism/antagonism). We confirmed that some progestins could elicit estrogenic effects in fish brain. In mixtures, EE2 and LNG exerted additive estrogenic effects both in vitro and in vivo, suggesting that some environmental progestin could exert effects that will add to those of environmental (xeno-)estrogens. Moreover, our zebrafish specific assays are valuable tools that could be used in risk assessment for both single chemicals and their mixtures.
Databáze: OpenAIRE
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