Large-scale analysis of acute ethanol exposure in zebrafish development: a critical time window and resilience
- Authors
- Ali, S., Champagne, D.L., Alia, A., and Richardson, M.K.
- ID
- ZDB-PUB-110609-29
- Date
- 2011
- Source
- PLoS One 6(5): e20037 (Journal)
- Registered Authors
- Richardson, Michael
- Keywords
- Embryos, Ethanol, Edema, Zebrafish, Yolk sac, Eyes, Cartilage, Microphthalmia
- MeSH Terms
-
- Animals
- Ethanol/administration & dosage
- Ethanol/toxicity*
- Female
- Magnetic Resonance Spectroscopy
- Male
- Teratogens/toxicity*
- Time Factors
- Zebrafish/embryology*
- PubMed
- 21625530 Full text @ PLoS One
BACKGROUND:
In humans, ethanol exposure during pregnancy causes a spectrum of developmental defects (fetal alcohol syndrome or FAS). Individuals vary in phenotypic expression. Zebrafish embryos develop FAS-like features after ethanol exposure. In this study, we ask whether stage-specific effects of ethanol can be identified in the zebrafish, and if so, whether they allow the pinpointing of sensitive developmental mechanisms. We have therefore conducted the first large-scale (>1500 embryos) analysis of acute, stage-specific drug effects on zebrafish development, with a large panel of readouts.
METHODOLOGY/PRINCIPAL FINDINGS:
Zebrafish embryos were raised in 96-well plates. Range-finding indicated that 10% ethanol for 1 h was suitable for an acute exposure regime. High-resolution magic-angle spinning proton magnetic resonance spectroscopy showed that this produced a transient pulse of 0.86% concentration of ethanol in the embryo within the chorion. Survivors at 5 days postfertilisation were analysed. Phenotypes ranged from normal (resilient) to severely malformed. Ethanol exposure at early stages caused high mortality (e88%). At later stages of exposure, mortality declined and malformations developed. Pharyngeal arch hypoplasia and behavioral impairment were most common after prim-6 and prim-16 exposure. By contrast, microphthalmia and growth retardation were stage-independent.
CONCLUSIONS:
Our findings show that some ethanol effects are strongly stage-dependent. The phenotypes mimic key aspects of FAS including craniofacial abnormality, microphthalmia, growth retardation and behavioral impairment. We also identify a critical time window (prim-6 and prim-16) for ethanol sensitivity. Finally, our identification of a wide phenotypic spectrum is reminiscent of human FAS, and may provide a useful model for studying disease resilience.