PUBLICATION

Monitoring estrogenic activities of waste and surface waters using a novel in vivo zebrafish embryonic (EASZY) assay: Comparison with in vitro cell-based assays and determination of effect-based trigger values

Authors
Brion, F., De Gussem, V., Buchinger, S., Hollert, H., Carere, M., Porcher, J.M., Piccini, B., Féray, C., Dulio, V., Könemann, S., Simon, E., Werner, I., Kase, R., Aït-Aïssa, S.
ID
ZDB-PUB-190614-16
Date
2019
Source
Environment International   130: 104896 (Journal)
Registered Authors
Keywords
Correlation, Effect-based trigger value, Estrogen monitoring, In vitro and in vivo bioassays, Zebrafish
MeSH Terms
  • Animals
  • Biological Assay
  • Embryo, Nonmammalian/drug effects*
  • Environmental Monitoring/methods*
  • Estradiol/analysis
  • Estradiol/toxicity
  • Estrogens*/analysis
  • Estrogens*/toxicity
  • Fresh Water/analysis*
  • Toxicity Tests
  • Water Pollutants, Chemical*/analysis
  • Water Pollutants, Chemical*/toxicity
  • Zebrafish
PubMed
31195222 Full text @ Environ. Int.
Abstract
This study reports the use of the recently developed EASZY assay that uses transgenic cyp19a1b-GFP zebrafish (Danio rerio) embryos to assess in vivo estrogenic activity of 33 surface (SW) and waste water (WW) samples collected across Europe that were previously well-characterized for estrogen hormones and in vitro estrogenic activity. We showed that 18 out of the 33 SW and WW samples induced estrogenic responses in the EASZY assay leading to a significant and concentration-dependent up-regulation of the ER-regulated cyp19a1b gene expression in the developing brain. The in vivo 17β-estradiol-equivalents (EEQs) were highly correlated with, both, the chemical analytical risk quotient (RQ) based on steroidal estrogen concentrations and EEQs reported from five different in vitro reporter gene assays. Regression analyses between the vitro and in vivo effect concentrations allowed us to determine an optimal cut-off value for each in vitro assay, above which in vivo responses were observed. These in vitro assay-specific effect-based trigger values (EBTs), ranging from 0.28 to 0.58 ng EEQ/L define the sensitivity and specificity of the individual in vitro assays for predicting a risk associated with substances acting through the same mode of action in water samples. Altogether, this study demonstrates the toxicological relevance of in vitro-based assessment of estrogenic activity and recommends the use of such in vitro/in vivo comparative approach to refine and validate EBTs for mechanism-based bioassays.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping