Role of growth factors on fetal growth and maturation.

Several growth factors have been demonstrated to be involved in fetal growth. In this study, physiological significance of two growth factors, epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) on fetal growth was evaluated. IGF-I stimulated 3H-glycine uptake by cultured trophoblast cells from term pregnancy while EGF did not stimulate it. A large part of IGF-I was associated with its binding proteins (IGFBPs) in the circulation and one of IGFBPs, IGFBP-1 inhibited 3H-glycine uptake by IGF-I in a dose dependent manner. IGF-I also stimulated 3H-aminoisobutyric acid (3H-AIB) release by trophoblast cells when cells were saturated with 3H-AIB first, then stimulated with IGF-I. In animal experiments, placental weight but not fetal weight was suppressed when EGF antiserum was administrated to maternal mice, however, fetal lung maturity in terms of lamella body produced in type II alveolar cells was suppressed in antiserum given group. When anti IGF-I antiserum was administrated to pregnant mice, both fetal and placental weight were significantly suppressed and transfer of 3H-AIB to fetus was also suppressed. In contrast, antiserum to IGFBP-1 stimulated fetal growth and transfer of 3H-AIB to fetus. Furthermore, fetal lung on Day 17 in anti IGFBP-1 antiserum administrated mice showed morphologically advanced changes that were equivalent to Day 18 or 19 of control. These results indicate that EGF and IGF-I regulate fetal growth and maturation independently and that IGF-I and IGFBP-1 influence fetal development in a counter regulatory system.