Non-Targeted Metabolomic Study of Fetal Growth Restriction

Abstract

We aimed to explore the differential metabolites in amniotic fluid and its cells from fetuses with fetal growth restriction (FGR). A total of 28 specimens of amniotic fluid were collected, including 18 with FGR and 10 controls. Differential metabolites in all samples were detected by chromatography–mass spectrometry. Principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used to analyze the differences in metabolic spectra between the FGR and control groups through multidimensional and single-dimensional statistical analysis. The KEGG database was used for metabolic pathway enrichment analysis. Both PCA and OPLS-DA models showed a clear separation trend between FGR and control groups. We identified 27 differentially expressed metabolites in the amniotic fluid supernatant of the two groups (p < 0.05), of which 14 metabolites were up-regulated in the FGR group, and 13 metabolites, such as glutamate, phenylalanine, valine and leucine, were down-regulated. We also identified 20 differentially expressed metabolites in the amniotic fluid cell (p < 0.05), of which 9 metabolites, including malic acid, glycolic acid and D-glycerate, were up-regulated significantly and 11 metabolites, including glyceraldehyde, were down-regulated. Pathway analysis showed that most of the identified differential metabolites were involved in tricarboxylic acid cycle (TCA cycle), ABC transport, amino acid metabolism pathways and so on. The results indicated that many metabolic changes associated with FGR, which are mainly manifested by abnormal metabolism of amino acid in amniotic fluid and abnormal glucose metabolism including TCA cycle in amniotic fluid cells, respectively. Our findings provide more data for exploring the mechanism of FGR and the potential therapy targets.