MATERNAL PROTEIN RESTRICTION EARLY OR LATE IN RAT PREGNANCY HAS DIFFERENTIAL-EFFECTS ON FETAL GROWTH, PLASMA INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) AND LIVER IGF-I GENE-EXPRESSION

We determined whether the effects of maternal protein restriction at various stages of pregnancy on fetal growth are accompanied by parallel changes in the expression of insulin-like growth factor (IGF)-I and -II in the fetal rat. Pregnant Wistar rats (5-7 per group) fed a low (5%) protein diet throughout gestation or during the last week only of gestation had decreased body weight gain, serum IGF-I, and liver IGF-I peptide and mRNA concentrations compared to control dams fed a normal (20%) protein diet. In contrast, dietary protein restriction during tbe first 2 weeks followed by the normal diet during the last week of pregnancy had no effect on these maternal indices at term. Pups born from dams fed the low protein diet during the last week only (P5-3(d) week pups) or throughout gestation (P5-pups) had lower birth weight (-11%; P<0.05, and -22%; P<0.001, respectively) and lower liver weight (-13%; P<0.05, and -29%; P<0.001) than control pups (P20-pups), Plasma IGF-I, liver IGF-I, and liver IGF-I mRNA concentrations were reduced in both P5-3(d) meek pups (by 34%, 31% and 26%, respectively) and P5-pups (by 56%, 66% and 44%, respectively). In contrast, short- or long-term maternal protein restriction had no effect on neonatal plasma IGF-II peptide and liver IGF-II mRNA concentrations. When imposed only during the first 2 weeks of gestation, maternal protein restriction had no effect on growth or IGF-I and IGF-II expression in newborn pups. Our results indicate that fetal growth and IGF-I synthesis are more dependent on maternal protein supply during rapid fetal growth (last week) than they are earlier in gestation (first 2 weeks). The parallel reductions observed in body weight and IGF-I gene expression of pups from protein-restricted dams suggest that IGF-I might be involved in the nutritional regulation of fetal growth.