Effects of acute prenatal ethanol administration in a reciprocal cross of C57BL/6J and short-sleep mice: maternal effects and nonmaternal factors.

ABSTRACT

An animal model was used to see if maternal genetic factors contribute to ethanol-induced fetal malformations. Susceptible C57BL/6J (B6) and resistant Short-Sleep (SS) mice were used in a reciprocal cross-breeding design. This design produced four fetal genotypes true-bred B6B6 and SSSS liters and hybrid B6SS and SSB6 litters. Dams were intubated with either 5.8 g/kg of ethanol or an isocaloric amount of maltose-dextrin on day 9 of pregnancy. Fetuses were removed on day 18 of pregnancy and assessed for soft tissue and gross malformations. Results show different prenatal treatment effects on malformations depending on the fetal genotype. Mean percentage of total malformations in ethanol-treated groups were 61% (B6B6), 28% (B6SS), 3% (SSB6), and 16% (SSSS), respectively. Litters exposed to maltose-dextrin showed low (< or = 4%) malformation rates regardless of fetal genotype. The difference in teratogenic response between genetically identical hybrid litters (B6SS and SSB6) suggests a maternal genetic contribution to susceptibility. Of the two major types of malformations, forelimb but not kidney malformations showed a pattern characteristic of a maternal genetic effect. It was concluded that maternal genetic effects can be distinguished from fetal genetic effects responsible for ethanol teratogenesis. Genetically based physiological responses to alcohol in the mother may confer varying degrees of risk for prenatal alcohol effects in the child.