# Epigenetic, histological and clinical characterization of preeclampsia in oocyte donation pregnancies: insights into immune dysregulation and microRNA-mediated pathways

## TL;DR

This study explores how immune and miRNA changes in oocyte donation pregnancies contribute to preeclampsia, revealing potential biomarkers for diagnosis and treatment.

## Contribution

The study identifies distinct miRNA and immune profiles in preeclamptic oocyte donation pregnancies, offering new insights into immune dysregulation and fetal protection mechanisms.

## Key findings

- Preeclamptic oocyte recipients showed upregulated pro-inflammatory miRNAs and cytokines, indicating immune activation.
- miRNA expression in umbilical cord plasma was inversely correlated with maternal and placental profiles, suggesting fetal protection mechanisms.
- Placental histology in oocyte donation preeclampsia showed milder changes compared to spontaneous cases, indicating different pathogenic processes.

## Abstract

Preeclampsia (PE) is a hypertensive disorder in pregnancy, influencing global health risks due to its poorly understood aetiology involving immune mismatches. Oocyte Donation increases PE risk due to complete HLA incompatibility, leading to immune activation. MicroRNAs (miRNAs) emerged as crucial regulators in placental development, immune regulation, and endothelial function, acting as post-transcriptional gene regulators. This study aims to explore whether specific miRNAs, previously implicated in PE, can be used to distinguish preeclamptic and non-preeclamptic mothers undergoing oocyte donation pregnancy.

This prospective study enrolled 20 mothers, divided into four groups: oocyte donation normotensive, oocyte donation preeclamptic, spontaneous normotensive, and spontaneous preeclamptic mothers. Maternal and cord blood samples were collected postpartum, along with placental biopsies. Tissue samples underwent histological examination. Total miRNAs were extracted from plasma, cord blood, and placenta and quantified via digital droplet PCR. The secretome analysis of cytokine/chemokines was performed on the mother’s plasma and cord blood by Luminex ELISA.

In oocyte normotensive the epigenetic (miR-155, miR-17, miR-30) and immune profile (CXCL10, VEGF), displayed only limited variations compared to spontaneous normotensive. Conversely, preeclamptic oocyte recipients exhibited marked molecular dysregulation, characterized by significant upregulation of pro-inflammatory miRNAs (miR-155, miR-17, miR-223) and cytokines (IL-6, IL-1β, TNF-α, IFN-γ) in maternal plasma and placental tissue, indicating heightened immune activation. Notably, miR-30 and let-7c were downregulated. Intriguingly, miRNA expression in umbilical cord plasma was often inversely correlated with maternal and placental profiles, suggesting complex miRNA trafficking and fetal protection mechanisms. Placental histology showed minimal pathological changes in preeclamptic oocyte recipients, contrasting with more severe lesions in preeclamptic spontaneously conceived pregnancies, reflecting differing underlying pathogenic processes.

This study highlights significant alterations in miRNA expression and cytokine profiles associated with PE, particularly in oocyte donation pregnancies. The findings suggested a complex interplay between maternal immune regulation and placental function, with distinct maternal and fetal immune responses. Understanding these molecular and immunological changes may facilitate the development of novel diagnostic biomarkers and targeted therapies to improve maternal and fetal outcomes in PE.

Diagram illustrating a three-step process. Step 1: Enrollment of various pregnancy types, including normotensive oocyte recipients and preeclamptic pregnancies. Step 2: Collection of biological samples like mother's plasma, cord's plasma, placenta, and placenta biopsy. Step 3: Functional analysis including cytokine/chemokine analysis, miRNA evaluation, and histological analysis.