Nakatsuji N, Johnson K E
Teratology. 1984 Jun;29(3):369-75. doi: 10.1002/tera.1420290307.
Recent studies of mouse models have suggested that malformations associated with the fetal alcohol syndrome (FAS) are caused by the effects of ethanol on early embryos during gastrulation and neurulation. A study of Xenopus laevis embryos showed that exposure of gastrula stage amphibian embryos to ethanol inhibits migration of the mesodermal cells, causes formation of small neural plates, and subsequently causes hypoplastic craniofacial malformations in tadpoles. We now report effects of ethanol on the primitive streak stage mouse embryos. An ethanol solution (25%) was injected intraperitonealy twice into mice of 6.5-7.0 days of pregnancy at a dose of 0.015 ml/gm of body weight. Histological and morphometric examinations of 7.5-day embryos, 20 hr after the second injection, showed that the epiblast layer was disorganized and shrunk with formation of many blebs. In addition, formation of the mesodermal cell layer was retarded in the ethanol-treated embryos, suggesting that exposure of gastrula stage embryos to ethanol causes similar abnormalities in mouse and Xenopus embryos. These results suggest that the inhibition of the morphogenetic movements during gastrulation may be the primary effect of ethanol in causing major craniofacial malformations of FAS.
近期对小鼠模型的研究表明，与胎儿酒精综合征（FAS）相关的畸形是由乙醇在原肠胚形成和神经胚形成期间对早期胚胎的影响所导致的。一项对非洲爪蟾胚胎的研究显示，将原肠胚阶段的两栖类胚胎暴露于乙醇中会抑制中胚层细胞的迁移，导致小神经板的形成，并随后在蝌蚪中引起颅面发育不全畸形。我们现在报告乙醇对原条期小鼠胚胎的影响。将25%的乙醇溶液以0.015 ml/g体重的剂量腹腔注射到怀孕6.5 - 7.0天的小鼠体内两次。在第二次注射后20小时对7.5天胚胎进行组织学和形态计量学检查，结果显示上胚层层紊乱并收缩，形成许多小泡。此外，在乙醇处理的胚胎中，中胚层细胞层的形成延迟，这表明将原肠胚阶段的胚胎暴露于乙醇会在小鼠和非洲爪蟾胚胎中引起类似的异常。这些结果表明，原肠胚形成期间形态发生运动的抑制可能是乙醇导致FAS主要颅面畸形的主要作用。
