Whole-transcriptome sequencing uncovers core regulatory modules and gene signatures of human fetal growth restriction

Guiying Wang,Xiaoqin Liu,Jiuhong Kang,Tao Duan,Xiaobo Zhao,Yiwei Yang,Xudong Guo,Chenqi Lu,Jun Yu

doi:10.1186/s40169-020-0259-0

Abstract

BackgroundFetal growth restriction (FGR) contributes the primary cause of perinatal mortality and morbidity with impacts on the long-term health. To determine the core gene expression network and gene signatures, which in combination with ultrasound confirmation will more effectively differentiate constitutionally normal small for gestational age and pathological FGR groups, we performed RNA sequencing for protein-coding genes, lncRNAs, and small RNAs in a case–control study of umbilical cord blood.ResultsFive pairs of FGR case and control umbilical cord blood samples were used for RNA sequencing and weighted gene co-expression network analysis (WGCNA). Results showed that 339 mRNAs, 295 lncRNAs, and 13 miRNAs were significantly differentially expressed between FGR cases and controls. Bioinformatics analysis indicated that these differentially expressed molecules were mainly involved in metabolism, neural, cardiac, and immune systems, and identified 18 WGCNA modules for FGR. Further quantitative verification was performed using umbilical cord blood and maternal peripheral blood from 12 pairs of FGR cases and controls. The logistic regression and receiver operating characteristic curve indicated that RP11_552M6.1, LINC01291, and Asgr1 in umbilical cord blood, while Sfrp2, miR-432-5p, and miR-1306-3p in maternal peripheral blood had potential significance for FGR.ConclusionsWe comprehensively profiled the whole-transcriptome landscape of human umbilical cord blood with FGR, constructed the core WGCNA modules, and delineated the critical gene signatures of FGR. These findings provide key insight into intrauterine perturbations and candidate signatures for FGR.

Highlights

Fetal growth restriction (FGR) contributes the primary cause of perinatal mortality and morbidity with impacts on the long-term health
Different transcriptome of FGR and control umbilical cord blood To examine differences in the entire transcriptome between FGR cases and normal controls, we performed RNA sequencing for protein-coding genes, long noncoding RNAs (lncRNAs), and miRNAs in a case–control study with five pairs of umbilical cord blood samples (Additional file 1: Table S1)
The differential expression analysis and hierarchical clustering showed that the protein-coding genes mostly tended to be down-regulated (Fig. 1a), while the lncRNAs (Fig. 1b) and miRNAs (Fig. 1c) tended to be up-regulated in the FGR cases as compared to the corresponding controls

Summary

Introduction

Fetal growth restriction (FGR) contributes the primary cause of perinatal mortality and morbidity with impacts on the long-term health. Fetal growth restriction (FGR) is a common pregnancy complication that occurs in 5–10% of all pregnancies. FGR is the primary cause of perinatal mortality and morbidity, and has impacts on the long-term health of the offspring [1,2,3]. Children surviving FGR are at a greater risk of developing neurodevelopmental dysfunction during childhood and cardiovascular and/or metabolic diseases subsequently in life [4]. Individuals with FGR have a higher tendency to develop obesity [6]. Late-onset FGR, which occurs after 32 weeks of gestation, is more complicated, results in fewer characteristic histological changes and has an unknown underlying mechanism [9]. Timely and accurate prenatal detection of FGR remains challenging

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Discussion

Conclusion