Long-term suppression of insulin-like growth factor-1 in rats after in utero ethanol exposure: relationship to somatic growth

Abstract

It has been established that consumption of alcohol during pregnancy has profound developmental and behavioral effects on the fetus and offspring. The present studies were undertaken to examine the consequences of in utero ethanol exposure on the regulation of insulin-like growth factors (IGFs) in relation to observed somatic growth deficits. Ad libitum, pair- and ethanol-fed female rats were maintained on liquid diet from day 2 of pregnancy through parturition. Pups were sacrificed at birth or cross-fostered to nonexperimental mothers and sacrificed at 10, 20 and 40 days of age. Body and brain weights of ethanol-exposed pups were reduced compared to either ad libitum or pair-fed animals; however, brain to body weight ratios were not different between groups. In ethanol-treated offspring, plasma IGF-1 concentrations were reduced 14 to 40% compared to ad libitum or pair-fed animals at birth, 10 and 20 days of age, with a nonsignificant reduction observed at 40 days of age. Plasma IGF-2 concentrations were not different between any treatment group at any age, suggesting that the ethanol-induced reduction in IGF-1 was a selective effect of prenatal ethanol exposure. Although IGF-binding proteins were generally not affected before 20 days in prenatally exposed rats, significant reductions were observed in 20- and 40-day-old ethanol-exposed pups. These results suggest that long-term reductions in plasma IGF-1 concentrations contribute to the reduced body and brain weights observed in ethanol-treated pups, and lend further support to the importance of the IGF and IGF-binding proteins in pre- and postnatal growth and development.