Cytoplasmic factors do not contribute to a maternal effect on ethanol teratogenesis
Cytoplasmic factors do not contribute to a maternal effect on ethanol teratogenesis
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DOI：
10.1023/a:1021485821842
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发表时间：
1999-01-01
影响因子：
2.6
通讯作者：
Gilliam, D
中科院分区：
文献类型：
--
作者：
Downing, C;Gilliam, D
母体和胎儿的遗传因素都会影响胎儿对酒精暴露的反应。为评价母体基因对乙醇致畸的影响，采用动物模型对相对易感的C57BL/6J(B6)和相对抗病的DBA/2J(D2)近交系小鼠进行了正反交研究。这种交配模式产生了四种胚胎基因型：真正繁殖的B6B6和D2D2窝仔以及杂交的B6D2和D2B6窝仔。为了研究母体卵细胞质作为可解释母体效应的变异源的作用，将B6D2和D2B6F1雌性与B6雄性交配，这产生了两个额外的胚胎基因型：B6D2.B6和D2B6.B6。在怀孕第9天，用5.8克/公斤的乙醇或等卡路里的麦芽糖-糊精插管。在怀孕的第18天，处死母猪，取出胎儿，称量体重，进行性别鉴定，并检查是否有严重的形态畸形。每一窝中的其他胎儿都被准备进行骨骼或软组织分析。结果显示，B6D2组的畸胎率高于遗传相似的D2B6组，这表明母体基因对乙醇致畸的易感性有影响。受影响的男性和女性胎儿的比例没有差异，这表明与性别有关的因素并不是造成母体影响的原因。回交后代B6D2.B6和D2B6.B6在任何致畸指标上都没有显著差异，这表明母体传递的细胞质物质的差异不是母体效应的原因。可能解释母体效应的因素是母体子宫环境和基因组印记的差异。为了识别处于危险中的母亲和婴儿，需要将导致乙醇致畸的母婴机制从母体中分离出来。
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 Fl 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 ethahol teratogenesis is needed for identifying mothers and infants at risk.