PRENATAL ETHANOL-CONSUMPTION ALTERS THE EXPRESSION OF CELLULAR RETINOL-BINDING PROTEIN AND RETINOIC ACID RECEPTOR MESSENGER-RNA IN FETAL-RAT EMBRYO AND BRAIN

The mechanism by which prenatal ethanol ingestion causes fetal alcohol syndrome (FAS) is unknown. We hypothesize that ethanol disrupts the n ormal function of retinoids in embryogenesis and differentiation, resu lting in FAS. The present work was designed to determine if prenatal e thanol ingestion affects the expression of cellular retinol binding pr otein (CRBP) and nuclear retinoic acid receptors (RARs). Paired timed pregnant rats were fed a liquid diet, one group treated with 36% of ca rbohydrate calories replaced with ethanol. Maternal serum retinol conc entrations during pregnancy peaked on the 6th day of pregnancy, but no difference was noted between the ethanol and control group. At the 12 th and 20th day of gestation, embryos or fetal brain were removed, and RNA was isolated for Northern hybridization. The abundance of CRBP mR NA was significantly elevated by ethanol consumption in both the 12-da y embryo (relative density of control: 1.00 +/- 0.10; vs. ethanol: 1.8 7 +/- 0.30, p < 0.05) and 20-day fetal brain (relative density of cont rol: 1.00 +/- 0.09; vs. ethanol: 1.46 +/- 0.09, p < 0.01). In the embr yo, 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), b ut had no effect on RAR-alpha or RAR-gamma mRNA. In contrast to the em bryo, 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 ra ts (3.7-kb RAR-alpha control: 1.00 +/- 0.11; vs. ethanol: 1.65 +/- 0.0 6; p < 0.001;2.7-kb RAR-alpha control: 1.00 +/- 0.14; vs. ethanol: 1.7 4 +/- 0.27, p < 0.05), whereas RAR-beta and RAR-gamma expression were not altered. These observations suggest that altered vitamin A functio n is a potential factor in the embryopathy of prenatal ethanol exposur e.