Placental Microarray Profiling Reveals Common mRNA and lncRNA Expression Patterns in Preeclampsia and Intrauterine Growth Restriction.

Diana Medina-Bastidas,César Ruiz-Cruz,Guadalupe Estrada-Gutierrez,Mario Guzmán-Huerta,Arturo Flores-Pliego,Sandra Parra-Hernández,Ivan Salido-Guadarrama,Hector Borboa-Olivares,Lisbeth Camargo-Marín,Eliakym Arambula-Meraz

doi:10.3390/ijms21103597

Abstract

Preeclampsia (PE) and Intrauterine Growth Restriction (IUGR) are major contributors to perinatal morbidity and mortality. These pregnancy disorders are associated with placental dysfunction and share similar pathophysiological features. The aim of this study was to compare the placental gene expression profiles including mRNA and lncRNAs from pregnant women from four study groups: PE, IUGR, PE-IUGR, and normal pregnancy (NP). Gene expression microarray analysis was performed on placental tissue obtained at delivery and results were validated using RTq-PCR. Differential gene expression analysis revealed that the largest transcript variation was observed in the IUGR samples compared to NP (n = 461; 314 mRNAs: 252 up-regulated and 62 down-regulated; 133 lncRNAs: 36 up-regulated and 98 down-regulated). We also detected a group of differentially expressed transcripts shared between the PE and IUGR samples compared to NP (n = 39), including 9 lncRNAs with a high correlation degree (p < 0.05). Functional enrichment of these shared transcripts showed that cytokine signaling pathways, protein modification, and regulation of JAK-STAT cascade are over-represented in both placental ischemic diseases. These findings contribute to the molecular characterization of placental ischemia showing common epigenetic regulation implicated in the pathophysiology of PE and IUGR.

Highlights

IntroductionPreeclampsia (PE) and Intrauterine Growth Restriction (IUGR) are two of the great obstetrical syndromes that are significant contributors to maternal and perinatal morbidity and mortality [1]
Preeclampsia (PE) and Intrauterine Growth Restriction (IUGR) are two of the great obstetrical syndromes that are significant contributors to maternal and perinatal morbidity and mortality [1].These pregnancy disorders carry severe health consequences for both mother and fetus, when they manifest together [2]
Forty-five pregnant women with intact membranes, no clinical evidence of intrauterine infection, singleton pregnancy, and who delivered by cesarean section (C-section) with no evidence of active labor were included in the study and divided into four study groups: intrauterine growth restriction (IUGR, n = 12), preeclampsia with severe features (PE, n = 11), preeclampsia with intrauterine growth restriction (PE-IUGR, n = 11) and normal pregnancy (NP, n = 11), this last group was constituted by women with uncomplicated pregnancies at term who delivered normal weight newborns

Summary

Introduction

Preeclampsia (PE) and Intrauterine Growth Restriction (IUGR) are two of the great obstetrical syndromes that are significant contributors to maternal and perinatal morbidity and mortality [1]. These pregnancy disorders carry severe health consequences for both mother and fetus, when they manifest together [2]. The placenta is a transient organ that fulfills key tasks to ensure nourishment and oxygen diffusion for the developing fetus. It works as a waste filtration system and as a fetal protective barrier. The impaired capacity of the trophoblast to invade uterine spiral arteries causes blood flow resistance, placental damage, hypoxia, acute atherosis, immune modifications and oxidative stress that lead to impaired cell function, release of proinflammatory cytokines, selective suppression of protein synthesis in the endoplasmic reticulum and apoptosis

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