PUBLICATION
Transcriptomic effects of tributyltin (TBT) in zebrafish eleutheroembryos. A functional benchmark dose analysis
- Authors
- Martínez, R., Codina, A.E., Barata, C., Tauler, R., Piña, B., Navarro-Martín, L.
- ID
- ZDB-PUB-200601-17
- Date
- 2020
- Source
- Journal of hazardous materials 398: 122881 (Journal)
- Registered Authors
- Piña, Benjamin
- Keywords
- Benchmark dose, Endocrine disruption, RNA-Seq, Tributyltin, Zebrafish
- Datasets
- GEO:GSE139599
- MeSH Terms
-
- Animals
- Benchmarking
- Transcriptome
- Trialkyltin Compounds*/toxicity
- Water Pollutants, Chemical*/toxicity
- Zebrafish/genetics
- PubMed
- 32474318 Full text @ J. Hazard. Mater.
Citation
Martínez, R., Codina, A.E., Barata, C., Tauler, R., Piña, B., Navarro-Martín, L. (2020) Transcriptomic effects of tributyltin (TBT) in zebrafish eleutheroembryos. A functional benchmark dose analysis. Journal of hazardous materials. 398:122881.
Abstract
Exposure to the antifouling tributyltin (TBT) has been related to imposex in mollusks and to obesogenicity, adipogenesis and masculinization in fish. To understand the underlying molecular mechanisms, we evaluated dose-response effects of TBT (1.7-56 nM) in zebrafish eleutheroembryos transcriptome exposed from 2 to 5 days post-fertilization. RNA-sequencing analysis identified 3238 differentially expressed transcripts in eleutheroembryos exposed to TBT. Benchmark dose analyses (BMD) showed that the point of departure (PoD) for transcriptomic effects (9.28 nM) was similar to the metabolomic PoD (11.5 nM) and about one order of magnitude lower than the morphometric PoD (67.9 nM) or the median lethal concentration (LC50: 93.6 nM). Functional analysis of BMD transcriptomic data identified steroid metabolism and cholesterol and vitamin D3 biosynthesis as the most sensitive pathways to TBT (<50% PoD). Conversely, transcripts related to general stress and DNA damage became affected only at doses above the PoD. Therefore, our results indicate that transcriptomes can act as early molecular indicators of pollutant exposure, and illustrates their usefulness for the mechanistic identification of the initial toxic events. As the estimated molecular PoDs are close to environmental levels, we concluded that TBT may represent a substantial risk in some natural environments.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping