Gilliam David
School of Psychological Sciences, University of Northern Colorado Greeley, CO, USA.
Front Genet. 2014 Dec 11;5:436. doi: 10.3389/fgene.2014.00436. eCollection 2014.
Genetic factors influence fetal alcohol spectrum disorders (FASDs) in both humans and animals. Experiments using inbred and selectively bred mouse stocks that controlled for (1) ethanol dose, (2) maternal and fetal blood ethanol levels, and (3) fetal developmental exposure stage, show genotype can affect teratogenic outcome. Other experiments distinguish the teratogenic effects mediated by maternal genotype from those mediated by fetal genotype. One technique to distinguish maternal versus fetal genotype effect is to utilize embryo transfers. This study is the first to examine ethanol teratogenesis - fetal weight deficits and mortality, and digit, kidney, and vertebral malformations - in C57BL/6J (B6) and DBA/2J (D2) fetuses that were transferred as blastocysts into B6 and D2 dams. We hypothesized that, following maternal alcohol exposure, B6 and D2 fetuses gestating within B6 mothers, as compared to D2 mothers, will exhibit a higher frequency of malformations. On day 9 of pregnancy, females were intubated (IG) with either 5.8 g/kg ethanol (E) or maltose-dextrin (MD). Other females were mated within strain and treated with either ethanol or maltose, or were not exposed to either treatment. Implantation rates were affected by genotype. Results show more B6 embryos implanted into D2 females than B6 females (p < 0.05; 47% vs. 23%, respectively). There was no difference in the percentage of D2 embryos implanting into B6 and D2 females (14 and 16%, respectfully). Litter mortality averaged 24% across all experimental groups. Overall, in utero ethanol exposure reduced mean litter weight compared to maltose treatment (E = 1.01 g; MD = 1.19 g; p < 0.05); but maltose exposed litters with transferred embryos weighed more than similarly treated natural litters (1.30 g vs. 1.11 g; p < 0.05). Approximately 50% of all ethanol exposed B6 fetuses exhibited some malformation (digit, vertebral, and/or kidney) regardless of whether they were transferred into a B6 or D2 female, or were naturally conceived. This suggests the D2 maternal uterine environment did not offer any protection against ethanol teratogenesis for B6 fetuses. One of the questions remaining is the how the B6 uterine environment affects D2 teratogenesis. No definitive conclusions can be drawn because too few viable D2 litters were produced.
遗传因素在人类和动物中均会影响胎儿酒精谱系障碍（FASDs）。使用近交系和选择性培育的小鼠品系进行的实验，这些实验控制了（1）乙醇剂量、（2）母体和胎儿血液中的乙醇水平以及（3）胎儿发育暴露阶段，结果表明基因型会影响致畸结果。其他实验区分了母体基因型介导的致畸作用和胎儿基因型介导的致畸作用。一种区分母体与胎儿基因型效应的技术是利用胚胎移植。本研究首次在作为囊胚移植到B6和D2母鼠体内的C57BL/6J（B6）和DBA/2J（D2）胎儿中，研究乙醇致畸作用——胎儿体重不足和死亡率，以及手指、肾脏和脊柱畸形。我们假设，在母体酒精暴露后，与在D2母体内发育的胎儿相比，在B6母体内发育的B6和D2胎儿将表现出更高的畸形频率。在怀孕第9天，给雌性小鼠经口插管（IG）给予5.8 g/kg乙醇（E）或麦芽糖糊精（MD）。其他雌性小鼠在品系内交配，并给予乙醇或麦芽糖处理，或不接受任何处理。着床率受基因型影响。结果显示，植入D2雌性小鼠体内的B6胚胎比植入B6雌性小鼠体内的更多（p < 0.05；分别为47%和23%）。植入B6和D2雌性小鼠体内的D2胚胎百分比没有差异（分别为14%和16%）。所有实验组的窝仔死亡率平均为24%。总体而言，与麦芽糖处理相比，子宫内乙醇暴露降低了平均窝仔体重（E = 1.01 g；MD = 1.19 g；p < 0.05）；但移植胚胎的麦芽糖暴露窝仔比同样处理的自然窝仔体重更重（1.30 g对1.11 g；p < 0.05）。所有乙醇暴露的B6胎儿中约50%表现出某种畸形（手指、脊柱和/或肾脏），无论它们是移植到B6还是D2雌性小鼠体内，或是自然受孕。这表明D2母体子宫环境并未为B6胎儿提供任何抵御乙醇致畸作用的保护。剩下的问题之一是B6子宫环境如何影响D2致畸作用。由于产生的存活D2窝仔太少，无法得出明确结论。
