Transcriptome alterations following developmental atrazine exposure in zebrafish are associated with disruption of neuroendocrine and reproductive system function, cell cycle, and carcinogenesis
- Authors
- Weber, G.J., Sepulveda, M.S., Peterson, S.M., Lewis, S.S., and Freeman, J.L.
- ID
- ZDB-PUB-130208-2
- Date
- 2013
- Source
- Toxicological sciences : an official journal of the Society of Toxicology 132(2): 458-466 (Journal)
- Registered Authors
- Freeman, Jennifer, Peterson, Sam
- Keywords
- atrazine, development, endocrine disruption, gene expression, transcriptomics, zebrafish
- Datasets
- GEO:GSE117398
- MeSH Terms
-
- Animals
- Atrazine/toxicity*
- Cell Cycle/drug effects*
- Cell Transformation, Neoplastic*
- Herbicides/toxicity*
- Neurosecretory Systems/drug effects*
- Reproduction/drug effects*
- Transcriptome*
- Zebrafish
- PubMed
- 23358194 Full text @ Toxicol. Sci.
- CTD
- 23358194
Atrazine, an herbicide commonly applied to agricultural areas and a common contaminant of potable water supplies, is implicated as an endocrine disrupting chemical (EDC) and potential carcinogen. Studies show that EDCs can cause irreversible changes in tissue formation, decreased reproductive potential, obesity, and cancer. The United States Environmental Protection Agency (USEPA) considers an atrazine concentration of d 3 ppb in drinking water safe for consumption. The specific adverse human health effects associated with a developmental atrazine exposure and the underlying genetic mechanisms of these effects are not well defined. In this study, zebrafish embryos were exposed to a range of atrazine concentrations to establish toxicity. Morphological, transcriptomic, and protein alterations were then assessed at 72 hours post fertilization (hpf) following developmental atrazine exposure at 0, 0.3, 3, or 30 ppb. A significant increase in head length was observed in all three atrazine treatments. Transcriptomic profiles revealed 21, 62, and 64 genes with altered expression in the 0.3, 3, and 30 ppb atrazine treatments, respectively. Altered genes were associated with neuroendocrine and reproductive system development, function, and disease; cell cycle control; and carcinogenesis. There was a significant overlap (42 genes) between the 3 and 30 ppb differentially expressed gene lists with two of these genes (CYP17A1 and SAMHD1) present in all three atrazine treatments. Increased transcript levels were translated to significant up-regulation in protein expression. Overall this study identifies genetic and molecular targets altered in response to a developmental atrazine exposure to further define the biological pathways and mechanisms of toxicity.