Grummer M A, Zachman R D
Department of Pediatrics, University of Wisconsin-Meriter Perinatal Center, Madison 53715, USA.
Alcohol Clin Exp Res. 1995 Dec;19(6):1376-81. doi: 10.1111/j.1530-0277.1995.tb00995.x.
The mechanism by which prenatal ethanol ingestion causes fetal alcohol syndrome (FAS) is unknown. We hypothesize that ethanol disrupts the normal function of retinoids in embryogenesis and differentiation, resulting in FAS. The present work was designed to determine if prenatal ethanol ingestion affects the expression of cellular retinol binding protein (CRBP) and nuclear retinoic acid receptors (RARs). Paired timed pregnant rats were fed a liquid diet, one group treated with 36% of carbohydrate calories replaced with ethanol. Maternal serum retinol concentrations during pregnancy peaked on the 6th day of pregnancy, but no difference was noted between the ethanol and control group. At the 12th and 20th day of gestation, embryos or fetal brain were removed, and RNA was isolated for Northern hybridization. The abundance of CRBP mRNA was significantly elevated by ethanol consumption. In both the 12-day embryo (relative density of control: 1.00 +/- 0.10; vs. ethanol: 1.87 +/- 0.30, p < 0.05) and 20-day fetal brain (relative density of control: 1.00 +/- 0.09; vs. ethanol: 1.46 +/- 0.09, p < 0.01). In the embryo, ethanol ingestion resulted in a decrease in the level of RAR-beta mRNA (control: 1.00 +/- 0.05; vs. ethanol: 0.71 +/- 0.07, p < 0.01), but had no effect on RAR-alpha or RAR-gamma mRNA. In contrast to the embryo, the expression of both the 3.7- and 2.7-kb RAR-alpha transcripts was significantly greater in day 20 fetal brain of ethanol-treated rats (3.7-kb RAR-alpha control: 1.00 +/- 0.11; vs. ethanol: 1.65 +/- 0.06; p < 0.001; 2.7-kb RAR-alpha control: 1.00 +/- 0.14; vs. ethanol: 1.74 +/- 0.27, p < 0.05), whereas RAR-beta and RAR-gamma expression were not altered. These observations suggest that altered vitamin A function is a potential factor in the embryopathy of prenatal ethanol exposure.
产前摄入乙醇导致胎儿酒精综合征（FAS）的机制尚不清楚。我们推测，乙醇会破坏胚胎发生和分化过程中视黄醇的正常功能，从而导致胎儿酒精综合征。本研究旨在确定产前摄入乙醇是否会影响细胞视黄醇结合蛋白（CRBP）和核视黄酸受体（RARs）的表达。将配对的定时怀孕大鼠喂食液体饲料，一组用36%的碳水化合物热量替换为乙醇。孕期母鼠血清视黄醇浓度在妊娠第6天达到峰值，但乙醇组和对照组之间未发现差异。在妊娠第12天和第20天，取出胚胎或胎儿大脑，分离RNA进行Northern杂交。乙醇消耗显著提高了CRBP mRNA的丰度。在12天的胚胎中（对照组相对密度：1.00±0.10；乙醇组：1.87±0.30，p<0.05）和20天的胎儿大脑中（对照组相对密度：1.00±0.09；乙醇组：1.46±0.09，p<0.01）均如此。在胚胎中，摄入乙醇导致RAR-β mRNA水平降低（对照组：1.00±0.05；乙醇组：0.71±0.07，p<0.01），但对RAR-α或RAR-γ mRNA没有影响。与胚胎相反，在乙醇处理大鼠的20天胎儿大脑中，3.7 kb和2.7 kb的RAR-α转录本表达均显著增加（3.7 kb RAR-α对照组：1.00±0.11；乙醇组：1.65±0.06；p<0.001；2.7 kb RAR-α对照组：1.00±0.14；乙醇组：1.74±0.27，p<0.05），而RAR-β和RAR-γ的表达未改变。这些观察结果表明，维生素A功能改变是产前乙醇暴露所致胚胎病的一个潜在因素。
