PUBLICATION
Phenotypically anchored transcriptome profiling of developmental exposure to the antimicrobial agent, triclosan, reveals hepatotoxicity in embryonic zebrafish
- Authors
- Haggard, D.E., Noyes, P.D., Waters, K.M., Tanguay, R.L.
- ID
- ZDB-PUB-160820-10
- Date
- 2016
- Source
- Toxicology and applied pharmacology 308: 32-45 (Journal)
- Registered Authors
- Tanguay, Robyn L.
- Keywords
- Hepatotoxicity, Phenotypic Anchoring, ToxCast, Transcriptomics, Triclosan, Zebrafish
- Datasets
- GEO:GSE80955
- MeSH Terms
-
- Animals
- Anti-Infective Agents, Local/pharmacology*
- Anti-Infective Agents, Local/toxicity
- Brain/metabolism
- Gene Expression Profiling*
- Gene Expression Regulation, Developmental/drug effects*
- Humans
- Liver/drug effects*
- Liver/metabolism
- Phenotype
- RNA, Messenger/metabolism
- Teratogens/toxicity
- Transcriptome*
- Triclosan/pharmacology*
- Triclosan/toxicity
- Zebrafish/embryology*
- Zebrafish/genetics
- PubMed
- 27538710 Full text @ Tox. App. Pharmacol.
- CTD
- 27538710
Citation
Haggard, D.E., Noyes, P.D., Waters, K.M., Tanguay, R.L. (2016) Phenotypically anchored transcriptome profiling of developmental exposure to the antimicrobial agent, triclosan, reveals hepatotoxicity in embryonic zebrafish. Toxicology and applied pharmacology. 308:32-45.
Abstract
Triclosan (TCS) is an antimicrobial agent commonly found in a variety of personal care products and cosmetics. TCS readily enters the environment through wastewater and is detected in human plasma, urine, and breast milk due to its widespread use. Studies have implicated TCS as a disruptor of thyroid and estrogen signaling; therefore, research examining the developmental effects of TCS is warranted. In this study, we used embryonic zebrafish to investigate the developmental toxicity and potential mechanism of action of TCS. Embryos were exposed to graded concentrations of TCS from 6 to 120h post-fertilization (hpf) and the concentration where 80% of the animals had mortality or morbidity at 120 hpf (EC80) was calculated. Transcriptomic profiling was conducted on embryos exposed to the EC80 (7.37μM). We identified a total of 922 significant differentially expressed transcripts (FDR adjusted p-value ≤0.05; fold change ≥2). Pathway and gene ontology enrichment analyses identified biological networks and transcriptional hubs involving normal liver functioning, suggesting TCS may be hepatotoxic in zebrafish. Tissue-specific gene enrichment analysis further supported the role of the liver as a target organ for TCS toxicity. We also examined the in vitro bioactivity profile of TCS reported by the ToxCast screening program. TCS had a diverse bioactivity profile and was a hit in 217 of the 385 assay endpoints we identified. We observed similarities in gene expression and hepatic steatosis assays; however, hit data for TCS were more concordant with the hypothesized CAR/PXR activity of TCS from rodent and human in vitro studies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping