Altered Placental and Fetal Expression of IGFs and IGF-Binding Proteins Associated With Intrauterine Growth Restriction in Fetal Sheep During Early and Mid-Pregnancy

The insulin-like growth factors (IGFs) are postulated to be altered in association with the development of intrauterine growth restriction (IUGR). The present studies examined placental and fetal hepatic mRNA concentration of components of the IGF system at two time points (55 and 90 d gestational age, dGA; Term 147 dGA) in a hyperthermia (HT)-induced sheep model of placental insufficiency-IUGR. Maternal plasma insulin and IGF-I were constant at 55 and 90 dGA and were unaffected by treatment. Umbilical vein insulin concentrations tended to be reduced at 90 dGA following HT exposure. Caruncle IGF-I mRNA was increased at 90 dGA in HT placentae (p < 0.05), while cotyledon concentrations were constant over gestation and unaltered by treatment. In control cotyledons, IGF-II mRNA concentration increased (p < 0.01) and IGFBP-3 decreased between 55 and 90 dGA (p < 0.01). Cotyledon IGF-II and caruncle IGFBP-4 mRNA were elevated at 55 dGA in HT placentae compared with control (p < 0.01 and p < 0.05 respectively). Fetal hepatic IGF-I, IGFBP-2, -3 and -4 concentrations rose over gestation (p < 0.05), but there were no treatment effects. These data suggest that changes in placental IGF expression in early and mid gestation may predispose the pregnancy to placental insufficiency, resulting in inadequate substrate supply to the developing fetus later in gestation.