# Common and recurrent dysregulated molecular network of placental hypoxia and associated vasculogenesis and angiogenesis in fetal growth restriction

## TL;DR

This study identifies a molecular network involving hypoxia and blood vessel formation in placental dysfunction linked to fetal growth restriction.

## Contribution

The study reveals a novel dysregulated molecular network involving HIF1A and VEGFA in placental hypoxia and angiogenesis in fetal growth restriction.

## Key findings

- 69 differentially expressed mRNAs and eight miRNAs were identified in FGR/sFGR placentae.
- HIF1A and VEGFA were key nodes in the molecular network related to hypoxia and angiogenesis.
- Upregulated HIF1A and VEGFA expression was validated and associated with clinical severity in sFGR twins.

## Abstract

Fetuses with fetal growth restriction (FGR) and selective FGR (sFGR) face elevated health risks both before and after birth. Although the underlying pathomechanisms remain unclear, placental dysfunction is recognized as a major contributing factor. By integrating untargeted transcriptomic data from FGR/sFGR placentae, this study identified 69 differentially expressed mRNAs (DEmRs) and eight differentially expressed miRNAs (DEmiRs). Functional enrichment analysis demonstrated significant enrichment in the angiogenesis and vasculogenesis pathways, with the hypoxia-related genes HIF1A and VEGFA serving as key nodes in the molecular network. Further validation through RNA sequencing (RNAseq), quantitative real-time PCR (RT-qPCR), and immunohistochemistry demonstrated that the expression of the transcriptional regulator HIF1A and the angiogenic factor VEGFA was upregulated in the placentae of sFGR twins and was significantly associated with clinical severity. Our results indicate that placental hypoxia, vasculogenesis, and angiogenesis via the molecular network of HIF1A and VEGFA may play an important role in the pathomechanisms of FGR and sFGR.