Teratogenic and behavioral anomalies induced by acute exposure of mice to ethanol and their possible relation to fetal brain DNA synthesis

Abstract

Physical and behavioral anomalies of fetal alcohol syndrome were studied after the i.p. administration of a single 3- or 6-g/kg dose of ethanol (25%, v/v) to gravid mice on either day 15 or day 18 of gestation. The physical effects of ethanol administered on either day 8, day 10, or day 12 of gestation (N = 6/group) were also examined and compared to the saline-administered controls. The identification of these anomalies and the effect of ethanol on the rate of fetal brain DNA synthesis were investigated. The physical anomalies were identified by standard procedures. Behavioral anomalies were measured as the inhibition of the development of various neonatal reflexes (N = 6-13/group) as compared to the saline-administered controls. The possible mechanism for these ethanol-induced abnormalities was identified by using [3H]thymidine to measure the rate of DNA synthesis (N = 6/group) in fetal mouse brains. Blood alcohol concentrations (N = 6/group) ranged from 410.2 mg/dl at 30 min to 25.8 mg/dl at 4.5 hr following the dosage of 3 g/kg of ethanol. Concentrations following the dosage of 6 g/kg of ethanol ranged from 753.7 mg/dl at 15 min to 127.1 mg/dl at 10.5 hr postinjection. Fetal and maternal weight gains were significantly inhibited compared to those of the controls. Various cranial facial, urogenital, skeletal, and cardiovascular anomalies were observed (P less than or equal to 0.05). Delays in the onset of the air and surface righting, visual placing, and negative geotaxis reflexes were observed for the ethanol-treated neonates, as compared to control values.(ABSTRACT TRUNCATED AT 250 WORDS)