Maternal genetic effects on ethanol teratogenesis and dominance of relative embryonic resistance to malformations.
Maternal genetic factors and/or fetal genetic factors contribute to variations in response to prenatal alcohol exposure. To assess the contribution of maternal genotype to ethanol teratogenesis, a reciprocal cross study was conducted in an animal model using C57BL/6J (B6) and long-sleep (LS) mice. B6 mice are more susceptible than LS mice to prenatal ethanol-induced malformations but both mouse stocks are susceptible to fetal weight deficits following in utero alcohol exposure. B6 and LS dams were reciprocally mated to B6 or LS males producing four embryonic genotype groups: the true-bred B6B6 and LSLS genotypes, and the genetically similar B6LS and LSB6 genotypes (the F1 genotype). Dams were intubated with either 5.8 g/kg ethanol (E) or an isocaloric amount of sucrose (S) on day 9 of pregnancy. Fetuses were removed on gestation day 18, weighed, and assessed for soft tissue or skeletal malformations. Results showed a greater litter weight deficit and increased total malformation rate in ethanol-exposed F1 litters carried by B6 mothers compared to ethanol-exposed F1 litters carried by LS mothers. This result would be expected only if maternal genetic factors contribute significantly towards susceptibility to ethanol teratogenesis. The influence of the LS mother was to decrease susceptibility to ethanol teratogenesis compared to the B6 mother while the influence of the B6 mother was to increase susceptibility to ethanol teratogenesis compared to the LS mother. The average malformation rate for F1 litters was significantly less than the predicted midparental value. This shows that the F1 genotype exhibited dominance towards resistance to prenatal alcohol effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Gilliam
D M
DM
Department of Psychology, University of Northern Colorado, Greeley 80639.
Irtenkauf
K T
KT
D000818:Animals; D001921:Brain / Q000002:abnormalities; D000431:Ethanol / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000235:genetics*; D005552:Forelimb / Q000002:abnormalities; D005838:Genotype; D007668:Kidney / Q000002:abnormalities; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D012307:Risk Factors; D015430:Weight Gain / Q000235:genetics
D000431:Ethanol