Differential Teratogenic Effect of Alcohol on Embryonic Development Between C57BL/6 and DBA/2 Mice: A New View

Abstract

BACKGROUND: Alcohol exposure during the fetal stage generates variable severity in different organs, as seen in fetal alcohol syndrome and fetal alcohol effect. Whether genetic factors or conditions of alcohol exposure influence the susceptibility to alcohol-related developmental impairment remains a question. METHODS: To investigate the contribution of genotype to the susceptibility to alcohol-induced toxicity during development beyond confounding maternal factors and variables of alcohol exposures, the authors tested the effect of alcohol exposure under definitive concentration using a whole embryonic culture of two inbred strains previously known to be vulnerable (C57BL/6 [C6]) or resistant (DBA/2 [D2]) to alcohol. On gestational day 8, embryos from each group bearing three to six somites were collected and then cultured for 44 hr in a medium added with 400 mg/dl of ethanol. The viability and morphological malformations, as well as developmental staging of the embryos, were all scored at the end of the culture. RESULTS: The authors found, in contrast to previous reports, that alcohol treatment retarded embryonic growth and induced abnormalities, including the neural tube opening and the hypoplasia of the optic vesicle in both strains. However, alcohol specifically compromised the heart and caudal neural tube in C6, whereas it specifically decreased the number of somites and the development of branchial bars among others in D2. CONCLUSIONS: These results demonstrated that both strains of embryos are vulnerable to the same amount and pattern of alcohol exposures at the same developmental stage, but each with unique vulnerability in specific organs, with alcohol having greater teratogenic effects in D2 than in C6. These differential vulnerabilities are results of greater genetic influence, rather than the maternal influence or conditions of alcohol.