Preeclampsia: The Interplay Between Oxygen-Sensitive miRNAs and Erythropoietin.

Vladislava Gusar,Oksana Vasilchenko,Angelika Timofeeva,Tatyana Ivanets,Kseniya Prozorovskaya,Vitaliy Chagovets,Gennadiy Sukhikh,Nataliya Kan

doi:10.3390/jcm9020574

Abstract

Changes in the oxygen partial pressure caused by a violation of uteroplacental perfusion are considered a powerful inducer of a cascade of reactions leading to the clinical manifestation of preeclampsia (PE). At the same time, the induction of oxygen-dependent molecule expression, in particular, miRNA and erythropoietin, is modulated. Therefore, the focus of our study was aimed at estimating the miRNA expression profile of placental tissue and blood plasma in pregnant women with preeclampsia using deep sequencing and quantitative RT-PCR, as well as determining the concentration of erythropoietin. The expression of miR-27b-3p, miR-92b-3p, miR-125b-5p, miR-181a-5p, and miR-186-5p, as regulated by hypoxia/reoxygenation, was significantly increased in blood plasma during early-onset preeclampsia. The possibility of detecting early PE according to the logistic regression model (miR-92b-3p, miR-125b-5p, and miR-181a-5p (AUC = 0.91)) was evaluated. Furthermore, the erythropoietin level, which is regulated by miR-125b-5p, was significantly increased. According to PANTHER14.1, the participation of these miRNAs in the regulation of pathways, such as the hypoxia’s response via HIF activation, oxidative stress response, angiogenesis, and the VEGF signaling pathway, were determined.

Highlights

Preeclampsia (PE) is a complication of pregnancy with characteristic symptoms: arterial hypertension, proteinuria, and peripheral edema [1,2]
Evaluation of the miRNA expression profile in placental tissue and blood plasma was performed using high-throughput sequencing on a HiSeq 2000 platform (Illumina, San Diego, CA, USA)
Given the multifactorial nature of the pathogenesis of PE, it is assumed that a specific miRNA repertoire is involved in the finely tuned network that regulates each link in this cascade—in particular, the link associated with hypoxia/reoxygenation

Summary

Introduction

Preeclampsia (PE) is a complication of pregnancy with characteristic symptoms: arterial hypertension, proteinuria, and peripheral edema [1,2]. PE occurs in about 2–8% of pregnancies and clinically manifests after 20 weeks of gestation. The leading hypotheses based on the multifactorial pathogenesis of PE associate the disorder with impaired trophoblast invasion into the myometrial segments of the spiral arteries, which leads to a decrease in uteroplacental blood flow and irregular perfusion of the placenta [3,4,5]. Hypoxia/reoxygenation occurs, leading to oxidative stress of the placenta—essentially in the endoplasmic reticulum compartment of the placental cells [6]. In late-onset PE (>34 weeks of gestation), diffuse placental hypoxia occurs for reasons not always associated with impaired placentation—in particular, due to overgrowing of the placenta, which leads to compression of the terminal villi, preventing perfusion [4,10]

Results

Discussion

Conclusion