Maternal Insulin-like Growth Factor-II Promotes Placental Functional Development Via the Type 2 IGF Receptor in the Guinea Pig

In guinea pigs, maternal insulin-like growth factor (IGF) infusion in early-pregnancy enhances placental transport near-term, increasing fetal growth and survival. The effects of IGF-II, but not IGF-I, appear due to enhanced placental labyrinthine (exchange) development. To determine if the type-2 IGF receptor (IGF2R) mediates these distinct actions of exogenous IGF-II in the mother, we compared the impact of IGF-II with an IGF-II analogue, Leu27-IGF-II, which only binds the IGF2R. IGF-II, Leu27-IGF-II (1 mg/kg per day.sc) or vehicle were infused from days 20–38 of pregnancy (term = 67 days) and placental structure and uptake and transfer of [3H]-methyl-d-glucose (MG) and [14C]-amino-isobutyric acid (AIB) and fetal growth and plasma metabolites, were measured on day 62. Both IGF-II and Leu27-IGF-II increased the volume of placental labyrinth, trophoblast and maternal blood space within the labyrinth and total surface area of trophoblast for exchange, compared to vehicle. Leu27-IGF-II also reduced the barrier to diffusion (trophoblast thickness) compared to vehicle and IGF-II. Both IGF-II and Leu27-IGF-II increased fetal plasma amino acid concentrations and placental transfer of MG to the fetus compared to vehicle, with Leu27-IGF-II also increasing AIB transport compared with vehicle and IGF-II. In addition, Leu27-IGF-II increased fetal weight compared to vehicle. In conclusion, maternal treatment with IGF-II or Leu27-IGF-II in early gestation, induce similar placental and fetal outcomes near term. This suggests that maternal IGF-II in early gestation acts in part via the IGF2R to persistently enhance placental functional development and nutrient delivery and promote fetal growth.