title: Screening estrogenic activities of chemicals or mixtures in vivo using transgenic (cyp19a1b-GFP) zebrafish embryos.
abstract: The tg(cyp19a1b-GFP) transgenic zebrafish expresses GFP (green fluorescent protein) under the control of the cyp19a1b gene, encoding brain aromatase. This gene has two major characteristics: (i) it is only expressed in radial glial progenitors in the brain of fish and (ii) it is exquisitely sensitive to estrogens. Based on these properties, we demonstrate that natural or synthetic hormones (alone or in binary mixture), including androgens or progestagens, and industrial chemicals induce a concentration-dependent GFP expression in radial glial progenitors. As GFP expression can be quantified by in vivo imaging, this model presents a very powerful tool to screen and characterize compounds potentially acting as estrogen mimics either directly or after metabolization by the zebrafish embryo. This study also shows that radial glial cells that act as stem cells are direct targets for a large panel of endocrine disruptors, calling for more attention regarding the impact of environmental estrogens and/or certain pharmaceuticals on brain development. Altogether these data identify this in vivo bioassay as an interesting alternative to detect estrogen mimics in hazard and risk assessment perspective.
authors.affiliation: 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.forename: François
authors.initials: F
authors.lastname: Brion
authors.forename: Yann
authors.initials: Y
authors.lastname: Le Page
authors.forename: Benjamin
authors.initials: B
authors.lastname: Piccini
authors.forename: Olivier
authors.initials: O
authors.lastname: Cardoso
authors.forename: Sok-Keng
authors.initials: SK
authors.lastname: Tong
authors.forename: Bon-chu
authors.initials: BC
authors.lastname: Chung
authors.forename: Olivier
authors.initials: O
authors.lastname: Kah
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D045166:Estradiol Congeners / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018716:Molecular Mimicry; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D045166:Estradiol Congeners; D029961:Zebrafish Proteins; D049452:Green Fluorescent Proteins; D004958:Estradiol; D001141:Aromatase; C440729:Cyp19a1a protein, zebrafish