# 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.

## Key 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.