Department of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Alcohol. 2010 Nov-Dec;44(7-8):659-71. doi: 10.1016/j.alcohol.2010.04.002. Epub 2010 Jun 8.
Alcohol consumption during pregnancy causes fetal alcohol spectrum disorder (FASD), which includes a range of developmental deficits. Fetal alcohol syndrome is the most severe form of FASD and can be diagnosed with pathognomonic facial features such as a smooth philtrum, short palpebral fissure, and thin upper vermilion. However, many children with developmental damage because of prenatal alcohol exposure exhibit none, or only a subset, of the above features, making diagnosis difficult. This study explored novel analyses to quantify the effect of a known dose of alcohol on specific facial measurements in substrains C57BL/B6J (B6J) and C57BL/6NHsd (B6N) mice. Mouse dams were provided alcohol (Alc) consisting of 4.8% (vol/vol) alcohol in a liquid diet for 16 days prepregnancy and chow and water diet during mating, and then the alcohol liquid diet was reinstated on gestational days 7 (E7) to gestational day 17 (E17). Treatment controls included a pair-fed (PF) group given matched volumes of an alcohol-free liquid diet made isocalorically and a group given ad lib access to lab chow and water (Chow). Maternal diet intake (Alc and PF), blood alcohol concentrations (BACs), embryo weights, and 15 morphometric facial measurements for E17 embryos were analyzed. B6N dams drank more alcohol during pregnancy and generated higher BAC than B6J dams. Both the Alc and PF treatments induced significant reductions in embryo weights relative to Chow in both substrains. Alcohol treatments produced significant changes, relative to controls, in 4 of the 15 facial measures for the B6N substrain but only in two measures for the B6J substrain. Discriminant analysis demonstrated successful classification of the alcohol-exposed versus nonalcohol-exposed B6N embryos, with a high sensitivity of 86%, specificity 80%, and overall classification (total correct 83%), whereas B6J mice yielded sensitivity of 80%, specificity 78%, and overall correct classification in 79%. In addition, B6N mice showed significantly more effects of pair feeding on these facial measures than did B6J mice, suggesting that the B6N substrain may be more vulnerable to nutritional stress during pregnancy. Overall, these data indicate that both B6N and B6J mice were vulnerable to alcohol but show differences in the severity and location of alcohol-induced dysmorphic facial features and may parallel findings from human studies comparing different ethnic groups. Furthermore, these findings suggest that discriminant analysis may be useful in predicting alcohol exposure in either mouse substrains.
怀孕期间饮酒会导致胎儿酒精谱系障碍（FASD），包括一系列发育缺陷。胎儿酒精综合征是 FASD 中最严重的形式，可以通过具有特征性的面部特征来诊断，例如光滑的人中、短的睑裂和薄的上唇。然而，许多因产前酒精暴露而发育受损的儿童没有表现出上述特征中的任何一个，或者只表现出其中的一部分，这使得诊断变得困难。本研究探索了新的分析方法，以量化已知剂量的酒精对 C57BL/B6J（B6J）和 C57BL/6NHsd（B6N）小鼠亚系特定面部测量值的影响。母鼠在受孕前 16 天接受含有 4.8%（体积/体积）酒精的液体饮食，在交配期间接受普通食物和水饮食，然后在受孕第 7 天（E7）至第 17 天（E17）重新开始酒精液体饮食。治疗对照组包括接受等量无酒精液体饮食的配对喂养（PF）组，该饮食通过热量匹配，以及接受普通食物和水（Chow）自由摄取的组。分析了 E17 胚胎的母鼠饮食摄入（Alc 和 PF）、血液酒精浓度（BAC）、胚胎重量和 15 项形态面部测量值。B6N 母鼠在怀孕期间饮酒量更多，BAC 高于 B6J 母鼠。在两个亚系中，Alc 和 PF 处理均导致胚胎重量相对于 Chow 显著降低。与对照组相比，酒精处理在 B6N 亚系的 15 项面部测量值中的 4 项中产生了显著变化，但在 B6J 亚系中仅在两项测量值中产生了变化。判别分析表明，酒精暴露与非酒精暴露的 B6N 胚胎的分类成功，敏感性为 86%，特异性为 80%，总体分类（总正确为 83%），而 B6J 小鼠的敏感性为 80%，特异性为 78%，总体正确分类为 79%。此外，B6N 小鼠在这些面部测量值上的配对喂养的影响明显大于 B6J 小鼠，这表明 B6N 亚系在怀孕期间可能更容易受到营养压力的影响。总体而言，这些数据表明，B6N 和 B6J 小鼠都容易受到酒精的影响，但在酒精引起的畸形面部特征的严重程度和位置上存在差异，这可能与比较不同种族人群的人类研究结果相平行。此外，这些发现表明，判别分析可能有助于预测这两种小鼠亚系中的酒精暴露。
