Developmental origins of neurotransmitter and transcriptome alterations in adult female zebrafish exposed to atrazine during embryogenesis

Wirbisky, S.E., Weber, G.J., SepĂșlveda, M.S., Xiao, C., Cannon, J.R., Freeman, J.L.
Toxicology   333: 156-67 (Journal)
Registered Authors
Freeman, Jennifer
atrazine, development, developmental origins of health and disease, neurotransmitters, transcriptomics, zebrafish
MeSH Terms
  • Age Factors
  • Animals
  • Atrazine/toxicity*
  • Brain/drug effects*
  • Brain/embryology
  • Brain/metabolism
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Endocrine Disruptors/toxicity*
  • Female
  • Gene Expression Profiling/methods
  • Gene Expression Regulation
  • Herbicides/toxicity*
  • Hydroxyindoleacetic Acid/metabolism*
  • Larva/drug effects
  • Larva/genetics
  • Larva/metabolism
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Risk Assessment
  • Serotonergic Neurons/drug effects*
  • Serotonergic Neurons/metabolism
  • Serotonin/metabolism*
  • Sex Factors
  • Time Factors
  • Transcriptome/drug effects*
  • Water Pollutants, Chemical/toxicity*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
25929836 Full text @ Toxicology
Atrazine is an herbicide applied to agricultural crops and is indicated to be an endocrine disruptor. Atrazine is frequently found to contaminate potable water supplies above the maximum contaminant level of 3μg/L as defined by the U. S. Environmental Protection Agency. The developmental origin of adult disease hypothesis suggests that toxicant exposure during development can increase the risk of certain diseases during adulthood. However, the molecular mechanisms underlying disease progression are still unknown. In this study, zebrafish embryos were exposed to 0, 0.3, 3, or 30μg/L atrazine throughout embryogenesis. Larvae were then allowed to mature under normal laboratory conditions with no further chemical treatment until 7 days post fertilization (dpf) or adulthood and neurotransmitter analysis completed. No significant alterations in neurotransmitter levels was observed at 7 dpf or in adult males, but a significant decrease in 5-Hydroxyindoleacetic acid (5-HIAA) and serotonin turnover was seen in adult female brain tissue. Transcriptomic analysis was completed on adult female brain tissue to identify molecular pathways underlying the observed neurological alterations. Altered expression of 1853, 84, and 419 genes in the females exposed to 0.3, 3, or 30μg/L atrazine during embryogenesis were identified, respectively. There was a high level of overlap between the biological processes and molecular pathways in which the altered genes were associated. Moreover, a subset of genes was down regulated throughout the serotonergic pathway. These results provide support of the developmental origins of neurological alterations observed in adult female zebrafish exposed to atrazine during embryogenesis.
Genes / Markers
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Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes