Cartwright M M, Smith S M
Department of Nutritional Sciences, University of Wisconsin-Madison 53706, USA.
Alcohol Clin Exp Res. 1995 Apr;19(2):378-86. doi: 10.1111/j.1530-0277.1995.tb01519.x.
Fetal alcohol syndrome (FAS) is characterized by growth retardation, craniofacial malformations, and heart and neural defects; the cellular and molecular mechanism(s) responsible for ethanol's teratogenicity remains unknown. Although the phenotype suggests that prenatal ethanol exposure perturbs neural crest cell development, direct proof that these cells are an in utero target is still lacking. Previous research suggested that cranial neural crest cells are eliminated by ethanol-induced apoptosis. We tested this hypothesis using a chick embryo model of FAS. A single dose of ethanol, chosen to achieve a concentration of 35-42 mg/dl, was injected in ovo at gastrulation and resulted in growth retardation, craniofacial foreshortening, and disrupted hindbrain segmentation. Ethanol exposure enhanced cell death within areas populated by cranial neural crest cells, particularly in the hindbrain and craniofacial mesenchyme. In contrast, control embryos had limited cell death within these regions. Subsequent immunolabeling with neural crest cell-specific antibody revealed that ethanol treatment resulted in fewer neural crest cell numbers, whereas neural crest migration patterns were unaffected by ethanol. These results suggest that prenatal ethanol exposure leads to loss of cranial neural crest cells. Such a loss could result, in part, in the phenotype characteristic of FAS.
胎儿酒精综合征（FAS）的特征为生长发育迟缓、颅面部畸形以及心脏和神经缺陷；乙醇致畸性的细胞和分子机制仍不明晰。尽管该综合征的表型提示产前乙醇暴露会干扰神经嵴细胞发育，但仍缺乏这些细胞是子宫内靶点的直接证据。先前的研究表明，颅神经嵴细胞会因乙醇诱导的凋亡而被清除。我们使用FAS的鸡胚模型对这一假说进行了验证。在原肠胚形成期向鸡胚卵内注射单剂量乙醇，使其浓度达到35 - 42毫克/分升，结果导致生长发育迟缓、颅面部缩短以及后脑节段化紊乱。乙醇暴露增强了颅神经嵴细胞所在区域的细胞死亡，尤其是在后脑和颅面部间充质中。相比之下，对照胚胎在这些区域的细胞死亡有限。随后用神经嵴细胞特异性抗体进行免疫标记显示，乙醇处理导致神经嵴细胞数量减少，而神经嵴迁移模式不受乙醇影响。这些结果表明产前乙醇暴露会导致颅神经嵴细胞丢失。这种丢失可能部分导致了FAS的特征性表型。
