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

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.

Identification of mRNA-, circRNA- and lncRNA- Associated ceRNA Networks and Potential Biomarkers for Preeclampsia From Umbilical Vein Endothelial Cells

“…In addition, the importance of the p53 and JAK/STAT signaling pathways was reconfirmed. There is no conflict with the former study that proved that p53 upregulation accelerated G1 arrest and apoptosis of HUVECs from preeclampsia patients (Gao et al, 2016), and a placenta microarray analysis also revealed the overrepresentation of the JAK/STAT pathway in PE (Medina-Bastidas et al, 2020), but little direct evidence explained the dysfunction of HUVECs from PE through the JAK/STAT pathway. Moreover, the following hub genes: CACNG8, LIPG, ACAA2, and OSMR, were shown to be involved in the ceRNA network.…”

Urothelial Cancer Associated 1 (UCA1) and miR-193 Are Two Non-coding RNAs Involved in Trophoblast Fusion and Placental Diseases

“…In about one third of the cases, PE is complicated with IUGR, suggesting that there could be an overlap in the etiology of both diseases. The considerable similarity in histopathology and gene expression in the placentas has been recently reported between both diseases ( Awamleh et al, 2019 ; Gibbs et al, 2019 ; Medina-Bastidas et al, 2020 ).…”

Sex-Biased lncRNA Signature in Fetal Growth Restriction (FGR)

“…Thus, to fully investigate FGR pathophysiology, both approaches to comparing placentas, within and between the sexes, should be performed. To validate the results of the current study, the obtained datasets were compared with recent similar projects [ 69 , 70 ]. In general, the expression tendencies were comparable, but the aforementioned projects lacked crucial information concerning the fetal sex of each sample.…”