Differential Distribution of Tryptophan-Metabolites in Fetal and Maternal Circulations During Normotensive and Preeclamptic Pregnancies

Preeclampsia (PE) is a hypertensive pregnancy, which is a leading cause of maternal and fetal morbidity and mortality during pregnancy. L-Tryptophan (Trp) is an essential amino acid, which can be metabolized into various biologically active metabolites. However, the levels of many circulating Trp-metabolites in human normotensive pregnancies (NT) and PE are undetermined. This study quantified the levels of Trp-metabolites in maternal and umbilical vein sera from women with NT and PE. Paired maternal and umbilical blood samples were collected from singleton pregnant patients. Twenty-five Trp-metabolites were measured in serum samples using liquid chromatography with tandem mass spectrometry. The effects of L-kynurenine (Kyn) and indole-3-lactic acid (ILA), on function of human umbilical vein endothelial cells (HUVECs), were also determined. Twenty Trp-metabolites were detected. The levels of 9 Trp-metabolites including Kyn and ILA were higher (P < 0.05) in umbilical vein than maternal serum, whereas 2 (5-hydroxy-L-tryptophan and serotonin) were lower (P < 0.05) in umbilical vein compared to maternal serum. PE significantly (P < 0.05) elevated ILA levels in maternal and umbilical vein sera. Kyn dose-dependently decreased (P < 0.05) cell viability. Kyn and ILA dose- and time-dependently (P < 0.05) increased monolayer integrity in HUVECs. These data suggest that these Trp-metabolites are important in regulating endothelial function during pregnancy, and the elevated ILA in PE may antagonize increased endothelial permeability occurring in PE.