EFFECTS OF MATERNAL PROTEIN-MALNUTRITION ON FETAL GROWTH, PLASMA INSULIN-LIKE GROWTH-FACTORS, INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS, AND LIVER INSULIN-LIKE GROWTH-FACTOR GENE-EXPRESSION IN THE RAT

We examined the effects of maternal dietary protein restriction on fet al growth and expression of IGF-I and -II, and IGF-binding proteins (I GFBP). We sought to dissociate the respective effects of maternal prot ein versus calorie restriction on growth indices and IGF synthesis by the neonates of protein-restricted dams. Pregnant Wistar rats (six to eight per group) fed a low (5%) protein diet throughout gestation had impaired body weight gain compared with controls fed a normal (20%) pr otein diet (by 45%, p < 0.001). Their serum and liver IGF-I concentrat ions and liver IGF-I mRNA concentrations were also reduced by 60, 80, and 50%, respectively. Serum IGFBP-3 was reduced by 60% in protein-res tricted dams within 1 to 2 h after delivery (p < 0.001 versus controls ), although IGFBP-1, -2, and -4 were not significantly affected by the dietary protein intake. In pups of protein-restricted dams, the mean body and liver weight at birth was 15-20% less than that observed in t he progeny from normal protein-fed dams (p < 0.01). Their plasma and l iver IGF-I concentrations were 30 and 60% lower, respectively, whereas liver IGF-I mRNA abundance was reduced by 50% (p < 0.01). In contrast , neonatal plasma IGF-II and liver IGF-II mRNA concentrations were not significantly affected by the maternal protein malnutrition. Also, th e plasma levels of IGFBP were not altered in the growth-retarded pups. Maternal protein restriction did not affect fetal and placental growt h, plasma and liver IGF-I levels, and liver IGF-I mRNA abundance in 20 -d-old fetuses. We conclude that intrauterine growth retardation cause d by maternal protein malnutrition is associated with reduced neonatal expression of the IGF-I gene without obvious changes in IGF-II gene e xpression and plasma IGFBP concentrations. These results support the e merging evidence that IGF-I may play a role in the regulation of fetal growth and development.