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 the incidence of ethanol teratogenesis, a reciprocal cross study was conducted 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 and D2B6 litters. To examine the role of maternal egg cytoplasm as the source of variation that could account for a maternal effect, B6D2 and D2B6 F1 females 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 of ethanol or an isocaloric amount of maltose-dextrin on day 9 of pregnancy. On day 18 of pregnancy, dams were sacrificed, fetuses were removed, weighed, sexed, and examined for gross morphological malformations. Every other fetus within a litter was prepared for either skeletal or soft tissue analysis. Results showed a higher rate of teratogenesis in the B6D2 group compared to the genetically similar D2B6 group, which indicates an influence of maternal 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 cytoplasmic material are not the cause of the maternal effect. Factors that could account for the maternal effect are differences in the maternal uterine environment and genomic imprinting. Separating maternal from fetal-mediated mechanisms responsible for susceptibility to ethanol teratogenesis is needed for identifying mothers and infants at risk.
Downing
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Psychology Department, State University of New York at Albany 12222, USA. CD8992@CNSVAX.ALBANY.EDU
Gilliam
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D000014:Abnormalities, Drug-Induced / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D002492:Central Nervous System Depressants / Q000633:toxicity*; D003433:Crosses, Genetic; D003593:Cytoplasm / Q000502:physiology; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000209:etiology; D000431:Ethanol / Q000633:toxicity*; D005111:Extrachromosomal Inheritance; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000235:genetics*; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010063:Ovum / Q000502:physiology; D011247:Pregnancy
D002492:Central Nervous System Depressants; D000431:Ethanol