G-Protein Coupled Receptor Dysregulation May Play Roles in Severe Preeclampsia—A Weighted Gene Correlation Network Analysis of Placental Gene Expression Profile

Abstract

Preeclampsia is one of the major hypertensive diseases of pregnancy. Genetic factors contribute to abnormal placentation. The inadequate transformation of cytotrophoblasts causes failure of maternal spiral arteries’ remodeling and results in narrow, atherotic-prone vessels, leading to relative placental ischemia. This study aims to explore the possibility of identifying dysregulated gene networks that may offer a potential target in the possible prevention of preeclampsia. We performed a weighted gene correlated network analysis (WGCNA) on a subset of gene expression profiles of placental tissues from severe preeclamptic pregnancies. We identified a gene module (number of genes = 402, GS = 0.35, p = 0.02) enriched for several G-protein-coupled receptor (GPCR)-related genes with significant protein–protein molecular interaction (number of genes = 38, FDR = 0.0007) that may play key roles in preeclampsia. Some genes are noted to play key roles in preeclampsia, including LPAR4/5, CRLR, NPY, TACR1/2, and SFRP4/5, whose functions generally relate to angiogenesis and vasodilation or vasoconstriction. Other upregulated genes, including olfactory and orexigenic genes, serve limited functions in the disease pathogenesis. Altogether, this study shows the utility of WGCNA in exploring possible new gene targets, and additionally reinforces the feasibility of targeting GPCRs that may offer intervention against development and disease progression among severe preeclampsia patients.