Placental insufficiency at mid-pregnancy, established through moderate maternal nutrient restriction, is characterized with fewer maternal spiral arteries lined by trophoblast, shallower trophoblast invasion and downregulation of genelists involved in the regulation of cell migration. Treatment of placenta insufficiency with a hIGF1 nanoparticle results in marked changes to transporter activity and increases our mechanistic understanding of how therapies designed to improve fetal growth may impact the placenta.