Altered distribution of fatty acid exerting lipid metabolism and transport at the maternal-fetal interface in fetal growth restriction

Introduction: Fetal growth restriction (FGR) is a common complication of pregnancy. Lipid metabolism and distribution may contribute to the progression of FGR. However, the metabolism-related mechanisms of FGR remain unclear. The aim of this study was to identify metabolic profiles associated with FGR, as well as probable genes and signaling pathways. Methods: Metabolomic profiles at the maternal-fetal interface (including the placenta, maternal and fetal serum) from pregnant women with (n = 35) and without (n = 35) FGR were analyzed by gas chromatography-mass spectrometry (GC-MS). Combined with differentially expressed genes (DEGs) from the GSE35574 dataset, analysis was performed for differential metabolites, and identified by the Metabo Analyst dataset. Finally, the pathology and screened DEGs were further identified. Results: The results showed that fatty acids (FAs) accumulated in the placenta and decreased in fetal blood in FGR cases compared to controls. The linoleic acid metabolism was the focus of placental differential metabolites and genes enrichment analysis. In this pathway, phosphatidylcholine can interact with PLA2G2A and PLA2G4C, and 12(13)-EpOME can interact with CYP2J2. PLA2G2A and CYP2J2 were elevated, and PLA2G4C was decreased in the FGR placenta. Discussion: In conclusion, accumulation of FAs in the placental ischemic environments, may involve linoleic acid metabolism, which may be regulated by PLA2G2A, CYP2J2, and PLA2G4C. This study may contribute to un-derstanding the underlying metabolic and molecular mechanisms of FGR.

Automated summary

Fetal growth restriction (FGR) is a common complication of pregnancy, and lipid metabolism may play a role in its development. However, the metabolic mechanisms of FGR are not well understood. This study used metabolomic profiling and gene analysis to identify metabolic profiles and potential genes and signaling pathways associated with FGR. The results showed that fatty acids accumulated in the placenta and decreased in fetal blood in FGR cases compared to controls, and linoleic acid metabolism was the focus of differential metabolite and gene enrichment analysis in the placenta.