MiRNAs Regulating Oxidative Stress: A Correlation with Doppler Sonography of Uteroplacental Complex and Clinical State Assessments of Newborns in Fetal Growth Restriction

Vladislava Gusar; Mariya Ganichkina; Vitaliy Chagovets; Nataliya Kan; Gennadiy Sukhikh

doi:10.3390/jcm9103227

MiRNAs Regulating Oxidative Stress: A Correlation with Doppler Sonography of Uteroplacental Complex and Clinical State Assessments of Newborns in Fetal Growth Restriction

J Clin Med. 2020 Oct 8;9(10):3227. doi: 10.3390/jcm9103227.

Authors

Vladislava Gusar¹, Mariya Ganichkina², Vitaliy Chagovets³, Nataliya Kan⁴, Gennadiy Sukhikh^{5

6}

Affiliations

¹ Laboratory of Applied Transcriptomics, Federal State Budget Institution "National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Healthcare of the Russian Federation", Oparin str. 4, 117997 Moscow, Russia.
² Obstetric Physiological Department, Federal State Budget Institution "National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Healthcare of the Russian Federation", Oparin str. 4, 117997 Moscow, Russia.
³ Laboratory of Proteomics and Metabolomics of Human Reproduction, Federal State Budget Institution "National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Healthcare of the Russian Federation", Oparin str. 4, 117997 Moscow, Russia.
⁴ Department for Obstetrics and Gynecology, Professional Education Department, Federal State Budget Institution "National Medical Research Center for Obstetrics, Gynecology and/Perinatology named after Academician V.I. Kulakov of the Ministry of Healthcare of the Russian Federation", Oparin str. 4, 117997 Moscow, Russia.
⁵ Federal State Budget Institution "National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Healthcare of the Russian Federation", Oparin str. 4, 117997 Moscow, Russia.
⁶ Department of Obstetrics, Gynecology, Perinatology and Reproductive Medicine, Institute of professional education, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Bolshaya Pirogovskaya str., 2, 119991 Moscow, Russia.

Abstract

Overproduction of reactive oxygen species (ROS) and, as a result, uncontrolled oxidative stress (OS) can play a central role in disorders of fetal hemodynamics and subsequent development of adverse perinatal outcomes in newborns with fetal growth restriction (FGR). Given the epigenetic nature of such disorders, the aim of our study was to evaluate the expression of miRNAs associated with OS and endothelial dysfunction (miR-27a-3p, miR-30b-5p, miR-125b-5p, miR-221-3p, miR-451a and miR-574-3p) in umbilical cord blood using real-time quantitative RT-PCR. ΜiRNA expression was evaluated in patients with FGR delivery before (n = 9 pregnant) and after 34 weeks of gestation (n = 13 pregnant), and the control groups corresponding to the main groups by gestational age (13 pregnant women in each group, respectively). A significant increase in miR-451a expression was detected in late-onset FGR and correlations with fetoplacental and cerebral circulation were established (increase of resistance in the umbilical artery (pulsatility index, PI UA (umbilical artery): r = -0.59, p = 0.001) and a decrease in cerebral blood flow (CPR: r = 0.48, p = 0.009)). The change in miR-125b-5p expression in the placenta is associated with reduced Doppler of cerebral hemodynamics (CPR: r = 0.73, p = 0.003; PI MCA (middle cerebral artery) : r = 0.79, p = 0.0007), and newborn weight (r = 0.56, p = 0.04) in early-onset FGR. In addition, significant changes in miR-125b-5p and miR-451a expression in umbilical cord blood plasma were found in newborns with neonatal respiratory distress syndrome (NRDS) (in early-onset FGR) and very low birth weight (VLBW) (in late-onset FGR). A number of key signaling pathways have been identified in which the regulation of the studied miRNAs is involved, including angiogenesis, neurotrophin signaling pathway and oxidative stress response. In general, our study showed that changes of the redox homeostasis in the mother-placenta-fetus system in FGR and subsequent perinatal outcomes may be due to differential expression of oxidative stress-associated miRNAs.

Keywords: Doppler; Fetal Growth Restriction/FGR; Pulsatility Index; fetal hemodynamics; microRNA/miRNA; oxidative stress; umbilical cord blood; vascular dysfunction.