Davenport, B.; Wilson, R.; Williams, A.; Gray, J.; Stanley, E. L.; Jones, H.

Fetal growth restriction (FGR) is most commonly due to placental insufficiency. There are currently no treatments for placental insufficiency or FGR, and the only intervention is iatrogenic pre-term delivery. We have previously shown efficacy of repeated placental nanoparticle-mediated insulin-like 1 growth factor (IGF1) treatment in improving placental efficiency (increased fetal-placental weight ratio) and correcting fetal growth in a maternal nutrient restriction (MNR) guinea pig model of FGR. Here we investigate the structural remodeling of the placenta following 3 repeated intraplacental injections of nanoparticle-mediated hIGF1 that may underpin the published improvements in placental efficiency and fetal growth. We hypothesize placenta structural changes (reduced exchange area, altered vascular structure) that we and others have previously shown in the FGR/MNR placenta which lead to deficits in placental function are mitigated by our repeated nanoparticle-mediated hIGF1 treatment. Sham-treated MNR placentas displayed disorganized microvasculature labyrinthine exchange areas with a reduction in placental capillary number and maternal blood space areas, and an increase in the volume of the placenta macrovasculature. Repeated nanoparticle-mediated hIGF1 treatment, however, resulted in an improved exchange area with normalized placental capillary number and maternal blood space area, and macrovasculature volume. This data demonstrates repeated nanoparticle-mediated hIGF1 delivery corrects aberrant placenta structure likely leading to improved gas exchange and transfer of nutrients to the fetus restoring fetal growth.