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 α, β and γ subtype message as expressed in mRNA. Levels of retinol and retinyl palmitate were significantly higher (p p α (3.7 kb) was increased (p β was decreased (p < 0.05) in the ethanol-exposed hearts. The alterations in endogenous retinoid levels and changes in the expression of certain retinoic acid receptor subtypes indicate a modulation in vitamin A metabolism caused by maternal ethanol ingestion and suggests a role of vitamin A in the pathogenesis of FAS.
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