Twal W O, Zile M H
Department of Food Science and Human Nutrition, Michigan State University, East Lansing 48824-1224, USA.
Alcohol Clin Exp Res. 1997 Sep;21(6):1137-43.
The effect of ethanol on early avian cardiovascular development was investigated in stage 8 quail embryos grown in culture for 24 hr. When the culture medium contained 1% ethanol, 50% of the embryos developed abnormalities of the cardiovascular system, some of which resembled vitamin A deficiency. Only 15% of the embryos grown in control media developed abnormalities attributed to the manipulation of the embryo. When all-trans-retinoic acid, the active form of vitamin A, was added at 10(-8) M to the ethanol-containing medium, the cardiovascular development was similar to that of untreated controls. Inclusion of 4-methylpyrazole and citral, enzyme inhibitors for the conversion of retinol to retinoic acid, produced cardiovascular abnormalities in embryos similar to those observed in vitamin A deficiency. These abnormalities were partially prevented by the presence of 10(-8) M all-trans-retinoic acid in the medium. Immunohistochemical studies using antibodies specific for the heart muscle myosin heavy chain (MF-20) and quail endothelial cells (QH-1) revealed that looping of the heart of ethanol-treated embryos was prevented, and the embryonal circulation had no or minimal vascular connections to the extraembryonic circulation. Our studies provide indirect evidence that ethanol is producing vitamin A deficiency during embryonic cardiovascular development and that these effects are specifically prevented by the presence of retinoic acid. These findings may explain some of the symptoms of fetal alcohol syndrome.
在体外培养24小时的第8期鹌鹑胚胎中，研究了乙醇对早期鸟类心血管发育的影响。当培养基中含有1%乙醇时，50%的胚胎出现心血管系统异常，其中一些类似于维生素A缺乏症。在对照培养基中培养的胚胎只有15%出现归因于胚胎操作的异常。当将维生素A的活性形式全反式视黄酸以10^(-8) M添加到含乙醇的培养基中时，心血管发育与未处理的对照相似。加入4-甲基吡唑和柠檬醛（视黄醇转化为视黄酸的酶抑制剂）会使胚胎出现与维生素A缺乏症中观察到的类似的心血管异常。培养基中存在10^(-8) M全反式视黄酸可部分预防这些异常。使用针对心肌肌球蛋白重链（MF-20）和鹌鹑内皮细胞（QH-1）的特异性抗体进行的免疫组织化学研究表明，乙醇处理的胚胎心脏的环化受到抑制，胚胎循环与胚外循环没有或只有极少的血管连接。我们的研究提供了间接证据，表明乙醇在胚胎心血管发育过程中导致维生素A缺乏，并且视黄酸的存在可特异性预防这些影响。这些发现可能解释胎儿酒精综合征的一些症状。
