Maternal nutrition and fetal growth: The role of insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs)

Maternal nutrition prior to and during pregnancy is an important determinant of fetal growth and size of the newborn. Reduction in fetal growth is a mechanism by which the fetus adapts to the unfavorable conditions to ensure its survival. Maternal undernutrition reduces fetal growth by altering the expression of paracrine growth factors, the most important of which are the insulin-like growth factors (IGFs) and their binding proteins. IGFs are potent mitogenic and differentiation factors which are expressed in multiple fetal tissues and placenta. IGFBPs modulate the interaction between IGFs and their receptors in an inhibitory manner under most circumstances. The reduction in cellular growth can therefore result from a decreased expression of IGFs or an increased expression of IGFBPs or both. Maternal undernutrition has been shown in several animal models to reduce IGF-I and increase IGFBP-1 concentrations in the fetal circulation. Since IGF-I and IGFBP-1 are synthesized predominantly in the fetal liver, we have utilized isolated fetal ovine hepatocytes to study the regulation of these genes by nutrition and hormones, and have demonstrated that the substrates (glucose) and hormones (insulin, catecholamines, and corticosteroids) have independent as well as dependent regulation of expression of these genes. Recently, fetal growth retardation due to maternal undernutrition has been shown to lead to longterm cardiovascular effects such as hypertension in adults, and therefore the adaptive response of the fetus in utero may cause not only immediate growth effects but also long-term consequences. The paracrine growth factors may play an important role in the pathophysiology of both short term and long-term consequences of fetal growth retardation.