# Fetal Neuronal Vesicles in the Assessment of Perinatal Brain Dysfunction and Late-Onset Growth Restriction: A Pilot Study

## TL;DR

This pilot study explores fetal neuronal vesicles in maternal blood as a potential early diagnostic tool for brain dysfunction and growth issues in fetuses with growth restriction.

## Contribution

The study introduces fetal neuronal vesicles as a novel 'fetal brain liquid biopsy' for assessing perinatal brain dysfunction and late-onset growth restriction.

## Key findings

- Altered levels of neurotrophic and presynaptic proteins were found in fetal neuronal vesicles from FGR pregnancies.
- Changes in sumoylation and neddylation proteins differ between early-onset and late-onset FGR.
- Increased SUMO2/3/4 levels may represent a neuroprotective response in late-onset FGR fetuses.

## Abstract

Fetal growth restriction (FGR) remains a significant problem in obstetrics and is a key risk factor for perinatal brain injury. The fetal neuronal vesicles (FNVs) isolated from maternal blood represent an innovative approach—a “fetal brain liquid biopsy”—enabling early diagnostics of neuronal dysfunction in FGR. Western blotting was used to evaluate the protein pattern expression of FNVs isolated from the blood of pregnant women with FGR and uncomplicated pregnancy. Significant changes in the neurotrophic proteins levels (pro-BDNF, pro-NGF) and presynaptic neurotransmission proteins (SYN1, SYP, SYNPO) were identified. New data were obtained on changes in the expression of proteins of sumoylation (SUMO2/3/4) and neddylation (NAE1, UBC12), which differs in early-onset and late-onset FGR. Moreover, increased SUMO2/3/4 levels can be considered as an endogenous neuroprotective response to cerebral hemodynamic reaction in fetuses with late-onset growth restriction. An association has been established between changes in the expression of the studied proteins and intraventricular hemorrhage (IVH) in newborns with late-onset growth restriction.