Cartwright M M, Smith S M
Department of Nutritional Sciences, University of Wisconsin-Madison 53706, USA.
Alcohol Clin Exp Res. 1995 Dec;19(6):1454-62. doi: 10.1111/j.1530-0277.1995.tb01007.x.
Fetal alcohol syndrome (FAS) is characterized by growth retardation, mental deficiencies, and numerous craniofacial and neuronal anomalies; the type and severity of these defects may be related to the time and dose of maternal ethanol exposure. Ethanol administered during presomitic stages results in the typical FAS craniofacial phenotype and is accompanied by a loss of cranial neural crest cells (CNCCs) through ethanol-induced cell death. However, the stage-specific effects of ethanol on the CNCC population is unknown. We examined the effects of ethanol on CNCC populations by treating in ovo chick embryos with a single ethanol dose (0.43 mmol/egg) at various stages of CNCC development, and corresponding to the first 3-4 weeks of human gestation. Ethanol treatment induced cell death and reduced CNCC populations in patterns consistent with observed dysmorphologies of CNCC-derived cranial structures. The precise population affected was dependent on the timing of ethanol exposure. Treatment at gastrulation or neurulation induced cell death and losses of CNCC populations, particularly those in rostral positions, and resulted in more severe craniofacial defects. In contrast, treatment at early somitic stages (4-16 somites) induced cell death, primarily within caudal CNCC populations, but resulted in less severe craniofacial defects, suggesting an increased capacity for recovery. These results suggest that there are distinct developmental windows during which the CNCCs may be particularly susceptible to ethanol-induced cell death. We conclude that ethanol exposure seems to affect specific events adversely during neural crest development. The timing of embryonic ethanol exposure relative to CNCC development could account, in part, for the heterogenous craniofacial defects observed in FAS.
胎儿酒精综合征（FAS）的特征为生长发育迟缓、智力缺陷以及众多颅面和神经元异常；这些缺陷的类型和严重程度可能与母体乙醇暴露的时间和剂量有关。在体节形成前阶段给予乙醇会导致典型的FAS颅面表型，并伴有通过乙醇诱导的细胞死亡导致的颅神经嵴细胞（CNCCs）丢失。然而，乙醇对CNCC群体的阶段特异性影响尚不清楚。我们通过在CNCC发育的各个阶段，即相当于人类妊娠的前3 - 4周，用单一乙醇剂量（0.43 mmol/蛋）处理鸡胚来研究乙醇对CNCC群体的影响。乙醇处理诱导细胞死亡并减少CNCC群体，其模式与观察到的源自CNCC的颅部结构的畸形一致。受影响的确切群体取决于乙醇暴露的时间。在原肠胚形成或神经胚形成阶段进行处理会诱导细胞死亡并导致CNCC群体减少，尤其是那些位于头侧位置的群体，并导致更严重的颅面缺陷。相比之下，在早期体节阶段（4 - 16体节）进行处理会诱导细胞死亡，主要发生在尾侧CNCC群体中，但导致的颅面缺陷较轻，这表明恢复能力增强。这些结果表明存在不同的发育窗口，在此期间CNCCs可能特别容易受到乙醇诱导的细胞死亡的影响。我们得出结论，乙醇暴露似乎会在神经嵴发育过程中对特定事件产生不利影响。胚胎乙醇暴露相对于CNCC发育的时间可能部分解释了在FAS中观察到的异质性颅面缺陷。
