Identification of a novel gene signature in second-trimester amniotic fluid for the prediction of preterm birth

Abstract

Preterm birth (PB) affects approximately 5–7% of live births worldwide and is the leading cause of neonatal morbidity and mortality. Amniotic fluid supernatant (AFS) contains abundant cell-free nucleic acids (cfNAs) that can provide genetic information associated with pregnancy complications. In the current study, cfNAs of AFS in the early second-trimester before the onset of symptoms of preterm birth were analyzed, and we compared the differentially expressed genes (DEGs) between PB (n = 5) and term birth (TB, n = 5) groups using sequencing analysis. Differential expression analyses detected 43 genes with increased and 11 genes with decreased expression in the PB group compared to TB. Upregulated expressions of RDH14, ZNF572, VOPP1, SERPINA12, and TCF15 were validated in an extended AFS sample by quantitative PCR (PB, n = 21; TB, n = 40). Five candidate genes displayed a significant increase in mRNA expression in immortalized trophoblast HTR-8/SVneo cell with H2O2 treatment. Moreover, the expression of five candidate genes was increased to more than 2-fold by pretreatment with lipopolysaccharide in HTR-8/SVneo cells. Alternation of gene expression between PB and TB is strongly correlated with oxidative stress and infection during pregnancy. It could be feasible diagnostic markers for early identification of women at risk of having PB.