Cytoplasmic factors do not contribute to a maternal effect on ethanol teratogenesis

Both maternal and fetal genetic factors influence variations in response to prenatal ethanol exposure. To assess the effect of maternal genotype on th e incidence of ethanol teratogenesis, a reciprocal cross study was conducte d in an animal mode using the relatively susceptible C57BL/6J (B6) and the relatively resistant DBA/2J (D2) inbred mice. This mating pattern produced four embryonic genotypes: true-bred B6B6 and D2D2 litters and hybrid B6D2 a nd D2B6 litters. To examine the role of maternal egg cytoplasm as the sourc e of variation that could account for a maternal effect, B6D2 and D2B6 Fl f emales were mated back to B6 males, which produced two additional embryonic genotypes: B6D2.B6 and D2B6.B6. Dams were intubated with either 5.8 g/kg o f ethanol or an isocaloric amount of maltose-dextrin on day 9 of pregnancy. On day 18 of pregnancy, dams were sacrificed, fetuses were removed, weighe d, sexed, and examined for gross morphological malformations. Every other f etus within a litter was prepared for either skeletal or soft tissue analys is. Results showed a higher rate of teratogenesis in the B6D2 group compare d to the genetically similar D2B6 group, which indicates an influence of ma ternal genotype on susceptibility to ethanol teratogenesis. The percentage of affected male and female fetuses did not differ, which suggests that sex -linked factors are not responsible for the maternal effect. The backcross B6D2.B6 and D2B6.B6 litters did not differ significantly for any measure of teratogenesis, suggesting that differences in maternally transmitted cytop lasmic material are not the cause of the maternal effect. Factors that coul d account for the maternal effect are differences in the maternal uterine e nvironment and genomic imprinting. Separating maternal from fetal-mediated mechanisms responsible for susceptibility to ethahol teratogenesis is neede d for identifying mothers and infants at risk.