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CHARACTERIZATION of EARLY LIFE EXPOSURE to ENVIRONMENTAL CHEMICALS and ITS IMPACTS on HEALTH School of Science and Technology Örebro University Sweden

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CHARACTERIZATION of EARLY LIFE EXPOSURE to ENVIRONMENTAL CHEMICALS and ITS IMPACTS on HEALTH School of Science and Technology Örebro University Sweden CHARACTERIZATION OF EARLY LIFE EXPOSURE TO ENVIRONMENTAL CHEMICALS AND ITS IMPACTS ON HEALTH School of Science and Technology Örebro University Sweden Lisanna Sinisalu Supervisors from Örebro University: Tuulia Hyötyläinen, Leo Yeung Examiner: Ingrid Ericson Jogsten Spring 2020 List of abbreviations 12-epiCA 3α, 7α, 12β-trihydroxy-5β-cholan-24-oic acid 12-oxo-LCA 12-oxolithocholic acid 18 18O2-PFHxS Perfluoro-1-hexane [ O2] sulfonic acid 4:2FTSA 4:2 fluorotelomer sulfonic acid 6:2 Cl-PFESA 6:2 chlorinated polyfluoroalkyl ether sulfonic acid 6:2FTSA 6:2 fluorotelomer sulfonic acid 7-oxo-DCA 7-oxodeoxycholic acid 7-oxo-HDCA 7-oxohyodeoxycholic acid 8:2 Cl-PFESA 8:2 chlorinated polyfluoroalkyl ether sulfonic acid 8:2FTSA 8:2 fluorotelomer sulfonic acid BA Bile acid CA Cholic acid CA-d4 Deuterated cholic acid CD Celiac disease CDCA Chenodeoxycholic acid CDCA-d4 Deuterated chenodeoxycholic acid CE Cholesterol ester Cer Ceramide CYP7A1 Cholesterol-7α-hydroxylase DCA Deoxycholic acid DCA-d4 Deuterated deoxycholic acid DG Diglyceride DHCA 3α,7α-dihydroxycholestanoic acid ECF Electrochemical fluorination FA Fatty acid FFA Free fatty acid FOSA Perfluorooctanesulfonamide GCA Glycocholic acid GCA-d4 Deuterated glycocholic acid GCDCA Glycochenodeoxycholic acid GCDCA-d4 Deuterated glycochenodeoxycholic acid GDCA Glycodeoxycholic acid GDHCA Glycodehydrocholic acid GHCA Glycohyocholic acid GHDCA Glycohyodeoxycholic acid GL Glycerolipid GLCA Glycolithocholic acid GLCA-d4 Deuterated glycolithocholic acid GP Glycerophospholipid GUDCA Glycoursodeoxycholic acid GUDCA-d4 Deuterated glycoursodeoxycholic acid HCA Hyocholic acid HDCA Hyodeoxycholic acid HPLC High-performance liquid chromatography ISTD Internal standard LCA Lithocholic acid 1 LCA-d4 Deuterated lithocholic acid LC-qTOF Liquid chromatography quadrupole time-of-flight LPC Lysophosphatidylcholine LPE Lysophosphatidylethanolamine L-PFBS Linear-perfluorobutane sulfonic acid L-PFDoS Linear -perfluorododecane sulfonic acid L-PFDS Linear-perfluorodecane sulfonic acid L-PFHpS Linear-perfluoroheptane sulfonic acid L-PFHxS Linear-perfluorohexane sulfonic acid L-PFNS Linear-perfluorononanoic sulfonic acid L-PFOS Linear-perfluorooctane sulfonic acid L-PFPeS Linear-perfluoropentane sulfonic acid 13 M2-6:2FTSA 1H, 1H, 2H, 2H-perfluoro-1-[1,2- C2] octane sulfonic acid 13 M2-8:2FTSA 1H, 1H, 2H, 2H-perfluoro-1-[1,2- C2] decane sulfonic acid 13 M2PFDA Perfluoro-n-[1,2- C2] decanoic acid 13 M2PFDoA Perfluoro-n-[1,2- C2] dodecanoic acid 13 M2PFHxA Perfluoro-n-[1,2- C2] hexanoic acid 13 M2PFHxDA Perfluoro-n-[1,2- C2] hexadecanoic acid 13 M2PFTeDA Perfluoro-n-[1,2- C2] tetradecanoic acid 13 M2PFUndA Perfluoro-n-[1,2- C2] undecanoic acid 13 M3PFBS Sodium perfluoro-1-[2,3,4- C3] butane sulfonic acid 13 M3PFPeA Perfluoro-n-[1,2,3- C3] pentanoic acid 13 M4PFBA Perfluoro-n-[1,2,3,4- C4] butanoic acid 13 M4PFHpA Perfluoro-n-[1,2,3,4- C4] heptanoic acid 13 M4PFOA Perfluoro-n-[ C8] octanoic acid 13 M4PFOS Sodium perfluoro-[ C8] octane sulfonic acid 13 M5PFNA Perfluoro-n-[ C9] nonanoic acid 13 M8FOSA-M Perfluoro-1-[ C8] octanesulfonamide NAFLD Non-alcoholic fatty-liver disease PC Phosphatidylcholine PC ether Phosphatidylcholine ether PE Phosphatidylethanolamine PE ether Phosphatidylethanolamine ether PFAS Per- and polyfluoroalkyl substances PFBA Perfluorobutanoic acid PFBS Perfluorobutane sulfonic acid PFDA Perfluorodecanoic acid PFDoDA Perfluorododecanoic acid PFDoDS Perfluorododecane sulfonic acid PFDS Perfluorodecane sulfonic acid PFHpA Perfluoroheptanoic acid PFHpS Perfluoroheptane sulfonic acid PFHxA Perfluorohexanoic acid PFHxDA Perfluorohexadecanoic acid PFHxS Perfluorohexane sulfonic acid PFNA Perfluorononanoic acid PFNS Perfluorononane sulfonic acid PFOA Perfluorooctanoic acid 2 PFOS Perfluorooctane sulfonic acid PFPeA Perfluoropentanoic acid PFPeS Perfluoropentan sulfonic acid PFTDA Perfluorotetradecanoic acid PFTeDA Perfluorotetradecanoic acid PFTriDA Perfluorotridecanoic acid PFUnDA Perfluoroundecanoic acid PI Phosphatidylinositols POPs Persistent organic pollutants PS Phosphatidyleserine RSD Relative standard deviation SM Sphingomyelins SP Sphingolipid ST Sterol lipid T1D Type 1 diabetes T2D Type 2 diabetes TCA Taurocholic acid TCA-d4 Deuterated taurocholic acid TCDCA Taurochenodeoxycholic acid TCDCA-d9 Deuterated taurochenodeoxycholic acid TDCA Taurodeoxycholic acid TDHCA Taurohyodeoxycholic acid TG Triglyceride TG mufa Triglyceride Monounsaturated fatty acids TG pufa Triglyceride Polyunsaturated fatty acids TG sfa Triglyceride Saturated fatty acids THCA Taurodeoxycholic acid THDCA Taurohyodeoxycholic acid TLCA Taurolithocholic acid TLCA-d4 Deuterated taurolithocholic acid TUDCA Tauroursodeoxycholic acid TUDCA-d4 Deuterated tauroursodeoxycholic acid TαMCA α-tauromuricholic acid TβMCA β-tauromuricholic acid TωMCA ω-tauromuricholic acid UDCA Ursodeoxycholic acid UDCA-d4 Deuterated ursodeoxycholic acid UHPLC- qTOF/MS Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry UNEP United Nations Environment Programme αMCA α-muricholic acid βMCA β-murocholic acid ωMCA ω-murocholic acid 3 Abstract The exposome is a complex study that includes both endogenous and exogenous markers related to different diseases as part of the research. Connecting both endogenous and exogenous markers can help explain many associations between environmental chemicals and metabolic profiles, which can be stressors for causing different diseases. This study investigates the impact of per- and polyfluorinated alkyl substances (PFAS) exposure during pregnancy on lipid profiles and measures the concentrations in blood and also in infants cord blood at birth. In addition, we are interested in lipids and bile acids (BA) levels in blood and if these three groups of analytes of interest are associated with each other. The infant blood-based samples come from a Chinese cohort and the maternal samples are from a Finnish cohort. The samples were extracted for PFAS and BA and for lipid analysis. Statistical analysis was performed for both cohorts. The main interest was to investigate the interactions between the identified compounds. The results also include concentrations to show the variety of values measured. Type 2 diabetes (T2D) and non-alcoholic fatty-liver disease (NAFLD) are usually not acquired early in life. Our results show a strong positive correlation between PFASs and triglycerides (TGs), as well as strong correlation between PFASs and conjugated primary and secondary BA particularly in cord blood samples, which can indicate higher risk of developing T2D or NAFLD. In maternal samples, the interactions between PFASs, BAs and lipids were much lower and showed less significant correlation. This indicates that the impact of PFAS exposure is much stronger during fetal development than in adult life. Acknowledgement The author of this study is thankful for support and help from Professor Tuulia Hyötyläinen and Dr. Leo Yeung. In addition, the author would like to thank Dr. Samira Salihovic and laboratory technician Daniel Duberg from Örebro University for guidance and help throughout the project. Professor Jia-Yin Dai and his students and staff from Chinese Academy of Sciences, the Institute of Zoology have given practical help and are being thanked for the support and kindness. The author is especially thankful for Jinghua Wang, from Chinese Academy of Sciences, for lots of practical help and for sharing a part of her research with this study. In addition, to FinnBrain cohort project for the cooperation. The author is grateful for Mobily grant provided by The Swedish Foundation for International Cooperation in Research and Higher Education (STINT) for the Joint China Sweden Mobility Programme 2018 (Dnr: CH2018-7805). 4 Table of content List of abbreviations .................................................................................................................. 1 Abstract ...................................................................................................................................... 4 Acknowledgement ..................................................................................................................... 4 Appendix list .............................................................................................................................. 7 1. Introduction ............................................................................................................................ 8 1.1 The exposome .................................................................................................................. 8 1.2 Per- and polyfluoroalkyl substances (PFASs) ................................................................. 8 1.3 Bile acids .......................................................................................................................... 9 1.4 Lipidomics ..................................................................................................................... 10 1.5 Impacts on health ........................................................................................................... 10 The aim ............................................................................................................................ 11 2. Materials and Methods ......................................................................................................... 12 2.1 Materials ............................................................................................................................ 12 Chemicals ............................................................................................................................
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