CIRCULATING INSULIN-LIKE GROWTH FACTOR-I AND FACTOR-II AND SUBSTRATESIN FETAL SHEEP FOLLOWING RESTRICTION OF PLACENTAL GROWTH

To determine the relationship between placental delivery of oxygen and glucose, circulating insulin-like growth factors (IGFs) and fetal gro wth, the effect of variable restriction of placental growth was determ ined in sheep in late gestation. Arterial blood was obtained via indwe lling catheters at 120 and 127 days of gestation, prior to necropsy at 130 days to measure fetal and placental weights. Plasma was acidified and subjected to size-exclusion high-performance liquid chromatograph y at pH 2.8 to dissociate and separate IGFs from their binding protein s. The acid-dissociated IGF fraction was analysed by sensitive and hig hly specific radioligand assays for IGF-I and IGF-II, previously defin ed using ovine IGFs. Fetal weight and blood pO(2) and glucose at 120 a nd 127 days of gestation correlated positively with placental weight. Plasma IGF-I was positively associated with fetal weight and fetal liv er weight, and with blood pO(2) and glucose at both ages. Plasma IGF-I I levels also correlated positively with fetal weight, fetal Liver wei ght and with blood glucose and pO(2), but only at 127 days of gestatio n. In the most severely growth-retarded fetal sheep, blood glucose and pO(2) and plasma IGF-I were significantly reduced when compared with normal fetuses at 120 days. All decreased further by 127 days of gesta tion as did plasma IGF-II in severely growth-retarded fetal sheep comp ared with normal fetuses. These observations are consistent with the h ypothesis that both IGF-I and IGF-II are chronically regulated by oxyg en and nutrition in utero and mediate part of the influence of placent al supply of substrate over fetal growth.