Eye-specific gene expression following embryonic ethanol exposure in zebrafish: Roles for heat shock factor 1
- Authors
- Kashyap, B., Pegorsch, L., Frey, R.A., Sun, C., Shelden, E.A., and Stenkamp, D.L.
- ID
- ZDB-PUB-140220-10
- Date
- 2014
- Source
- Reproductive toxicology (Elmsford, N.Y.) 43: 111-124 (Journal)
- Registered Authors
- Frey, Ruth, Shelden, Eric, Stenkamp, Deborah L.
- Keywords
- none
- Datasets
- GEO:GSE51427
- 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*
- 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
- PubMed
- 24355176 Full text @ Reprod. Toxicol.
- CTD
- 24355176
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.