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

Abstract

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.

• Authors: Bhavani Kashyap, Laurel Pegorsch, Ruth A Frey, Chi Sun, Eric A Shelden, Deborah L Stenkamp
• Journal: Reproductive toxicology (Elmsford, N.Y.) (Reprod Toxicol) Vol. 43 Pg. 111-24 (Jan 2014) ISSN: 1873-1708 [Electronic] United States
• PMID: 24355176 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

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