Aberrant placental structure is corrected with repeated nanoparticle-mediated IGF1 treatments in a Guinea pig model of fetal growth restriction

TL;DR

Repeated nanoparticle-mediated IGF1 treatments in guinea pigs correct placental structure and fetal growth issues caused by placental insufficiency.

Contribution

Repeated nanoparticle-mediated hIGF1 treatment corrects placental structural defects in a model of fetal growth restriction.

Findings

Sham-treated MNR placentas showed disorganized microvasculature and reduced capillary numbers.

Nanoparticle-mediated hIGF1 treatment normalized placental capillary number and macrovasculature volume.

Treatment improved placental structure, likely enhancing nutrient and gas exchange to the fetus.

Abstract

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. 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.

Here we investigate the structural remodeling of the placenta in a maternal nutrient restriction (MNR) guinea pig model following 3 repeated intraplacental injections of nanoparticle-mediated hIGF1 that may underpin the published improvements in placental efficiency and fetal growth. Using immunohistochemistry and Dice-CT we investigated the micro- and macrovasculature changes of the placenta structure to identify changes in FGR and treatment.

Sham-treated MNR placentas displayed disorganized microvasculature labyrinthine exchange areas with a reduction in placental capillary number 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 macrovasculature volume.

This data demonstrates repeated nanoparticle-mediated hIGF1 delivery corrects aberrant placenta structure during FGR and placental insufficiency likely leading to improved gas exchange and transfer of nutrients to the fetus restoring fetal growth.

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