Strain-dependent effects of developmental ethanol exposure in zebrafish.

摘要

Developmental ethanol exposure from maternal consumption of alcoholic beverages and many other consumer products has been linked to developmental abnormalities in humans and animal models. The sensitivity of an individual to ethanol-induced perturbation of developmental processes is strongly influenced by genetic factors. In this study, we show that there are strain- and dose-dependent differences in sensitivity to developmental ethanol exposure in zebrafish (Danio rerio), suggesting that genetic variation within regulatory factors, influencing critical developmental pathways, is responsible for these differences. Embryos/larvae from genetically distinct strains of zebrafish [Ekkwill (EK), AB, and Tuebingen (TU)] were treated with different concentrations of ethanol. Embryo/larval survival, neurocranial and craniofacial skeletal development, and CNS cell death were analyzed. EK was the most resistant strain to the embryolethal effects of ethanol exposure but had the greatest increase in ethanol-inducedcell death. AB survival was affected moderately, as were the neurocranial and craniofacial skeletal structures and ethanol-induced cell death. TU had the lowest survival rate but was the most resistant to alterations in neurocranial and craniofacial skeletal elements. No single strain is the most sensitive or the most resistant to any of the phenotypes examined, suggesting that alcohol influences each of these pathways independently. Further analysis of the molecular and biochemical pathways underlying the strain-dependent differences reported herein could lead to a significant advancement in our mechanistic understanding of the teratogenic effects of ethanol in humans.