Study Of Metabolomics Profiling In Maternal Hair And Plasama For Intrahepatic Cholestasis Of Pregnancy

PART Ⅰ STUDY OF METABOLOMICS PROFILING IN MATERNAL HAIR FOR INTRAHEPATIC CHOLESTASIS OF PREGNANCY FROM FIRST AND SECOND TRIMESTER OF PREGNANCYObjective: To investigate the hair metabolites of intrahepatic cholestasis of pregnancy(ICP)women in first and second trimester of pregnancy,and to explore targeted metabolites of ICP.Methods: 21 ICP pregnancies and 21 normal pregnancies were involved in the study.Maternal hair from first and second trimester of pregnancy were collected separately and the metabolomes were detected by gas chromatography-mass spectrometry(GC-MS).Results: A total of 164 metabolites were identified.Among them,only2 metabolites were significantly different between the two groups in first trimester of pregnancy(p < 0.05).Moreover,there were 19 metabolites identified in second trimester of pregnancy(p < 0.05).Among them,17 metabolites increased in ICP and 2 decreased.Glycine from metabolites of second trimester of pregnancy was the only metabolite that met PLS-DA model with variable influence on projection(VIP)value greater than 1 and p value less than 0.05.5 filtered metabolites from second trimester of pregnancy were obviously enriched in 7 pathways,including glyoxylate and dicarboxylate metabolism,aminoacyl-t RNA biosynthesis,citrate cycle,glutathione metabolism,glycine,serine and threonine metabolism and thiamine metabolism.Among the metabolites,glycine was involved in the functional regulation of 5 metabolic pathways.Conclusions: In this study,a total of 21 differential metabolites were identified(19 metabolites from second trimester of pregnancy and 2 from first trimester of pregnancy).Glycine was considered as the most potential metabolite.In addition,5 known differential metabolites from second trimester of pregnancy were mainly enriched in 7 pathways,and glycine was enriched in 5 metabolic pathways.PART Ⅱ STUDY OF METABOLOMICS PROFILING IN MATERNAL HAIR IN THIRD TRIMESTER OF PREGNANCY AND PLASMA FOR INTRAHEPATIC CHOLESTASIS OF PREGNANCYObjective: Compare the metabolite profiles of mother hair samples in third trimester of pregnancy and plasma from ICP and normal healthy subjects and investigate specific biomarkers for ICP from these two specimens.Methods: Pregnancy participants were recruited from Chongqing,China.After matching the BMI,gestational age,and age and removed other pregnancy complications,hair and plasma samples were collected from 35 ICP and 42 healthy pregnancies,and then analyzed by gas chromatography–mass spectrometry.Results: Among 164 and 155 metabolites identified in hair and plasma samples respectively,3 plasma metabolites(p < 0.05,q < 0.38)and21 hair metabolites(p < 0.05,q < 0.05)were significantly different between ICP and healthy pregnancies.There were eight hair metabolites with area under curve(AUC)≥ 0.80 discriminating ICP from normal pregnancies.By combining these eight hair metabolites into a multivariant ROC model showed the best AUC of 0.885,while plasma samples only exhibited the highest AUC about 0.74.Moreover,six and two hair metabolites displayed a significant positive(r > 0.5,p < 0.05)and negative (r <-0.5,p < 0.05)correlations with TBA levels.Importantly,there were six hair metabolites namely,cysteine,3-methyl-2-oxovaleric acid,2,4-Di-tert-butylphenol,histidine,β-Methylamino-alanine and DL-gamma-methyl-ketoglutaramate isomer 2 have ROC excessed 0.8 and correlation coefficient over 0.5 and less than-0.5.32 hair metabolic pathways,annotated into 13 biochemical classes,were significantly(p and q values less than 0.05)different between ICP and normal pregnancies,meanwhile no significant pathway was observed plasma.Furthermore,cysteine was involved in five significant metabolic pathways(including glutathione metabolism),histidine was involved in three significant metabolic pathways(including ABC transporter),and pyruvic acid was involved in significant center carbon metabolic pathways.In addition,the pollutants(DBP and BMAA)also increased significantly in hair metabolites.Conclusions: Hair metabolites can distinguish ICP and normal pregnancy better than plasma samples.The accumulations of cysteine,glycine,and histidine in maternal hair may indicate the dysregulation of glutathione metabolism and ABC transporter on the bile formation of ICP pregnancy.DBP and BMAA reflect that environmental pollutants may contribute to the pathophysiology of ICP.Thus,these prefunding hair metabolites could be potential biomarkers for the ICP diagnosis.