The effect of maternal ethanol ingestion on fetal rat heart vitamin A: a model for fetal alcohol syndrome.
Ethanol consumption during pregnancy can cause fetal alcohol syndrome (FAS). Although the exact mechanism is unknown, nutritional alterations caused by ethanol exposure may be an etiologic factor in FAS. The congenital heart defects seen in FAS are similar to those found in vitamin A teratogenesis. Because ethanol ingestion alters vitamin A metabolism, we hypothesized that the cardiac manifestations seen in FAS result from an alteration in vitamin A metabolism or function in the developing fetus. Twenty-day gestation fetal rat hearts from ethanol-exposed and control pregnancies were analyzed for 1) levels of endogenous retinol, retinyl palmitate, and retinoic acid by quantitative HPLC; 2) binding activity levels of both retinol by cellular retinol binding protein and retinoic acid by cellular retinoic acid binding protein using specific competitive binding assays; and 3) relative abundance of cellular retinol binding protein and retinoic acid receptor alpha, beta, and gamma subtype message as expressed in mRNA. Levels of retinol and retinyl palmitate were significantly higher (p < 0.01) and the level of retinoic acid was significantly lower (p < 0.02) in the ethanol-exposed fetal hearts. Binding activity levels of cellular retinol binding protein and cellular retinoic acid binding protein were not different in the two groups. The message for retinoic acid receptor alpha (3.7 kb) was increased (p < 0.01) and the message for retinoic acid receptor beta was decreased (p < 0.05) in the ethanol-exposed hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
DeJonge
M H
MH
Department of Pediatrics, University of Wisconsin, Meriter Hospital, Madison 53715, USA.
Zachman
R D
RD
D000818:Animals; D004195:Disease Models, Animal; D000431:Ethanol / Q000009:adverse effects*; D005069:Evaluation Studies as Topic; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000209:etiology* / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D008431:Maternal-Fetal Exchange; D009206:Myocardium / Q000378:metabolism; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014801:Vitamin A / Q000378:metabolism*
D014801:Vitamin A; D000431:Ethanol