Maternal-fetal interfaces transcriptome changes associated with placental insufficiency and a novel gene therapy...

Area of Science:

• Reproductive biology and developmental science.
• Genomics and molecular biology.
• Nanomedicine and drug delivery.

Background:

• Fetal growth restriction (FGR) often stems from placental insufficiency, characterized by inadequate trophoblast invasion, nutrient deficiency, and hypoxia.
• Current treatments for placental insufficiency and FGR are limited.
• A novel polymer-based nanoparticle for delivering human insulin-like 1 growth factor (hIGF1) has been developed for placental trophoblast gene expression.

Purpose of the Study:

• To investigate the molecular mechanisms underlying placental insufficiency using the guinea pig maternal nutrient restriction (MNR) model.
• To identify pathways in the sub-placenta/decidua affected by placental insufficiency.
• To evaluate the therapeutic potential of hIGF1 nanoparticle treatment in correcting these pathways.

Main Methods:

• Utilized the guinea pig MNR model to induce placental insufficiency and FGR.
• Administered ultrasound-guided hIGF1 nanoparticle treatment or sham treatment during mid-pregnancy.
• Performed transcriptome analysis via RNA sequencing on sub-placenta/decidua tissue collected 5 days post-treatment.

Main Results:

• MNR led to reduced trophoblast invasion and downregulated cell migration-related genes in the sub-placenta/decidua.
• hIGF1 nanoparticle treatment significantly altered transporter activity in MNR placentas compared to controls.
• In normal conditions, hIGF1 treatment modulated kinase signaling and proteolysis pathways, suggesting a role in maintaining homeostasis.

Conclusions:

• The study identified key transcriptomic changes in the sub-placenta/decidua contributing to inadequate trophoblast invasion in FGR.
• hIGF1 nanoparticle treatment demonstrates potential to restore placental function by targeting specific molecular pathways.
• This research enhances understanding of hIGF1's mechanism of action in treating placental insufficiency and FGR.