Prenatal ethanol consumption alters the expression of cellular retinol binding protein and retinoic acid receptor mRNA 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 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.
Grummer
M A
MA
Department of Pediatrics, University of Wisconsin-Meriter Perinatal Center, Madison 53715, USA.
Zachman
R D
RD
D000818:Animals; D001921:Brain / Q000196:embryology* / Q000473:pathology; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000235:genetics* / Q000473:pathology; D015870:Gene Expression / Q000502:physiology; D005865:Gestational Age; D008297:Male; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D012177:Retinol-Binding Proteins / Q000235:genetics*; D054840:Retinol-Binding Proteins, Cellular
D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular