Role of insulin-like growth factors in intrauterine and postnatal growth retardation caused by gestational protein malnutrition in the rat

In order to evaluate the hypothesis that nutrition-induced intrauterine and postnatal growth retardation could be due to alterations in insulin-like growth factors (IGFs) and their binding proteins (IGFBPs), we examined in a rat model the specific effects of maternal dietary protein restriction (25% of the protein intake of the control pregnant rats) on the growth indices of the progeny in relation to the effects on IGFs and IGFBPs.
The adverse effects of gestational protein malnutrition on fetal growth parallel changes in circulating fetal IGF-I; plasma IGF-I being normal in fetuses or neonates whose growth is not affected by maternal protein deficiency, and significantly reduced in the growth-retarded newborn pups. Furthemore, the reduction in plasma IGF-I of these pups reflects the degree of intrauterine growth retardation (IUGR), and is accompanied by parallel decreases in liver IGF-I peptide and mRNA. Taken together, our findings support the hypothesis that reductions on IGF-I production and/or availability contribute to stunting of fetal growth, and that decline in neonatal plasma IGF-I may be mediated through decreased expression of the IGF-I gene. In constrast, plasma IGF-II and liver IGF-II gene expression, plasma IGFBPs, insulin and GH cncentrations are not affected in the growth-retarded newborn pups after gestational protein malnutrition. Our studies, therefore, do not support a major role for IGF-II in the nutritional regulation of fetal growth, especially in nutrition-induced IUGR.
The long-term adverse of gestational protein malnutrition on postnatal growth of the progeny are also accompanied by parallel changes in circulating and liver concentrations of IGF-I, suggesting that this growth factor plays a pivotal role in the catch-up growth process after prenatal nutritional insult. There is, however, no concomitant alteration in liver IGF-I mRNA concentrations, serum IGFBPs, insulin and GH concentrations, suggesting that reduced IGF-I in these animals results more from a translational defect on IGF-I synthesis than from a persistent alteration of gene expression. Direct evidence for a role of IGF-I in postnatal growth retardation following IUGR is provided by our studies showing that restoration of normal serum IGF-I concentrations by exogenous IGF-I treatment in neonatal rats with IUGR and nutritional rehabilitation, induces postnatal catch-up growth. Similar effects are also observed under GH therapy which increases endogenous IGF-I production