Development of a Comprehensive Toxicity Pathway Model for 17α-Ethinylestradiol in Early Life Stage Fathead Minnows (Pimephales promelas)
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- estrogen, fathead minnow, histology, proteomics, toxicity pathway, transcriptomics,
- MeSH
- Water Pollutants, Chemical * toxicity MeSH
- Cyprinidae * MeSH
- Ethinyl Estradiol toxicity MeSH
- Proteomics MeSH
- Sex Differentiation MeSH
- Vitellogenins MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Water Pollutants, Chemical * MeSH
- Ethinyl Estradiol MeSH
- Vitellogenins MeSH
There is increasing pressure to develop alternative ecotoxicological risk assessment approaches that do not rely on expensive, time-consuming, and ethically questionable live animal testing. This study aimed to develop a comprehensive early life stage toxicity pathway model for the exposure of fish to estrogenic chemicals that is rooted in mechanistic toxicology. Embryo-larval fathead minnows (FHM; Pimephales promelas) were exposed to graded concentrations of 17α-ethinylestradiol (water control, 0.01% DMSO, 4, 20, and 100 ng/L) for 32 days. Fish were assessed for transcriptomic and proteomic responses at 4 days post-hatch (dph), and for histological and apical end points at 28 dph. Molecular analyses revealed core responses that were indicative of observed apical outcomes, including biological processes resulting in overproduction of vitellogenin and impairment of visual development. Histological observations indicated accumulation of proteinaceous fluid in liver and kidney tissues, energy depletion, and delayed or suppressed gonad development. Additionally, fish in the 100 ng/L treatment group were smaller than controls. Integration of omics data improved the interpretation of perturbations in early life stage FHM, providing evidence of conservation of toxicity pathways across levels of biological organization. Overall, the mechanism-based embryo-larval FHM model showed promise as a replacement for standard adult live animal tests.
Central European Institute of Technology Masaryk University Brno 625 00 Czech Republic
Computer Science Department St Francis Xavier University Antigonish Nova Scotia B2G 2W5 Canada
Department of Environment and Geography York University York YO10 5NG United Kingdom
Faculty of Agricultural and Environmental Sciences McGill University Montreal Quebec H9X 3V9 Canada
Global Institute for Food Security University of Saskatchewan Saskatoon Saskatchewan S7N 0W9 Canada
Global Institute for Water Security University of Saskatchewan Saskatoon Saskatchewan S7N 3H5 Canada
RECETOX Masaryk University Brno 625 00 Czech Republic
Toxicology Centre University of Saskatchewan Saskatoon Saskatchewan S7N 5B3 Canada
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