Eye-specific gene expression following embryonic ethanol exposure in zebrafish: roles for heat shock factor 1

Reprod Toxicol. 2014 Jan:43:111-24. doi: 10.1016/j.reprotox.2013.12.002. Epub 2013 Dec 16.


The mechanisms through which ethanol exposure results in developmental defects remain unclear. We used the zebrafish model to elucidate eye-specific mechanisms that underlie ethanol-mediated microphthalmia (reduced eye size), through time-series microarray analysis of gene expression within eyes of embryos exposed to 1.5% ethanol. 62 genes were differentially expressed (DE) in ethanol-treated as compared to control eyes sampled during retinal neurogenesis (24-48 h post-fertilization). The EDGE (extraction of differential gene expression) algorithm identified >3000 genes DE over developmental time in ethanol-exposed eyes as compared to controls. The DE lists included several genes indicating a mis-regulated cellular stress response due to ethanol exposure. Combined treatment with sub-threshold levels of ethanol and a morpholino targeting heat shock factor 1 mRNA resulted in microphthalmia, suggesting convergent molecular pathways. Thermal preconditioning partially prevented ethanol-mediated microphthalmia while maintaining Hsf-1 expression. These data suggest roles for reduced Hsf-1 in mediating microphthalmic effects of embryonic ethanol exposure.

Keywords: Ethanol; Eye; Fetal alcohol syndrome; Heat shock factor; Heat shock protein; Microarray; Retina; Zebrafish.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Embryo, Nonmammalian / drug effects
  • Embryo, Nonmammalian / metabolism
  • Ethanol / toxicity*
  • Eye / drug effects*
  • Eye / embryology
  • Eye / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental / drug effects*
  • Heat Shock Transcription Factors
  • Microphthalmos / chemically induced*
  • Microphthalmos / genetics
  • Microphthalmos / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Zebrafish / embryology
  • Zebrafish Proteins / genetics*
  • Zebrafish Proteins / metabolism


  • Heat Shock Transcription Factors
  • Transcription Factors
  • Zebrafish Proteins
  • hsf1 protein, zebrafish
  • Ethanol