PUBLICATION
Zebrafish embryos as a screen for DNA methylation modifications after compound exposure
- Authors
- Bouwmeester, M.C., Ruiter, S., Lommelaars, T., Sippel, J., Hodemaekers, H.M., van den Brandhof, E.J., Pennings, J.L., Kamstra, J.H., Jelinek, J., Issa, J.J., Legler, J., van der Ven, L.T.
- ID
- ZDB-PUB-151230-9
- Date
- 2016
- Source
- Toxicology and applied pharmacology 291: 84-96 (Journal)
- Registered Authors
- Legler, Juliette, van der Ven, Leo
- Keywords
- DNA methylation, Environmental contaminant exposure, Epigenetics, Screening, Zebrafish embryo
- MeSH Terms
-
- Animals
- Benzhydryl Compounds/toxicity
- DNA Methylation/drug effects*
- DNA Methylation/physiology
- Drug Evaluation, Preclinical/methods
- Embryo, Nonmammalian
- Epigenesis, Genetic/drug effects
- Epigenesis, Genetic/physiology
- Metals, Heavy/toxicity
- Phenols/toxicity
- Steroids/toxicity
- Zebrafish/embryology*
- Zebrafish/genetics*
- Zebrafish/metabolism
- Zebrafish Proteins/biosynthesis
- Zebrafish Proteins/genetics*
- PubMed
- 26712470 Full text @ Tox. App. Pharmacol.
- CTD
- 26712470
Citation
Bouwmeester, M.C., Ruiter, S., Lommelaars, T., Sippel, J., Hodemaekers, H.M., van den Brandhof, E.J., Pennings, J.L., Kamstra, J.H., Jelinek, J., Issa, J.J., Legler, J., van der Ven, L.T. (2016) Zebrafish embryos as a screen for DNA methylation modifications after compound exposure. Toxicology and applied pharmacology. 291:84-96.
Abstract
Modified epigenetic programming early in life is proposed to underlie the development of an adverse adult phenotype, known as the Developmental Origins of Health and Disease (DOHaD) concept. Several environmental contaminants have been implicated as modifying factors of the developing epigenome. This underlines the need to investigate this newly recognized toxicological risk and systematically screen for the epigenome modifying potential of compounds. In this study, we examined the applicability of the zebrafish embryo as a screening model for DNA methylation modifications. Embryos were exposed from 0 to 72h post fertilization (hpf) to bisphenol-A (BPA), diethylstilbestrol, 17α-ethynylestradiol, nickel, cadmium, tributyltin, arsenite, perfluoroctanoic acid, valproic acid, flusilazole, 5-azacytidine (5AC) in subtoxic concentrations. Both global and site-specific methylation was examined. Global methylation was only affected by 5AC. Genome wide locus-specific analysis was performed for BPA exposed embryos using Digital Restriction Enzyme Analysis of Methylation DREAM, which showed minimal wide scale effects on the genome, whereas potential informative markers were not confirmed by pyrosequencing. Site-specific methylation was examined in the promoter regions of three selected genes vasa, vtgI and cyp19a2, of which vasa (ddx4) was the most responsive. This analysis distinguished estrogenic compounds from metals by direction and sensitivity of the effect compared to embryotoxicity. In conclusion, the zebrafish embryo is a potential screening tool to examine DNA methylation modifications after xenobiotic exposure. The next step is to examine the adult phenotype of exposed embryos and to analyze molecular mechanisms that potentially link epigenetic effects and altered phenotypes, to support the DOHaD hypothesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping