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

BACKGROUND: Fetal 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. RESULTS: Five 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. CONCLUSIONS: We 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.