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.