Metabolome Wide Association Study of Serum Poly and Perfluoroalkyl Substances (PFASs) in Pregnancy and Early Postpartum

• Type of Material: Article
• Authors: Xin Hu, Emory University; Shuzhao Li, Emory University; Piera M. Cirillo, Public Health Institute; Nickilou Y. Krigbaum, Public Health Institute; Tran ViLinh, Emory University; Dean Jones, Emory University; Barbara A. Cohn, Public Health Institute
• Language: English
• Date: 2019-08-01
• Publisher: Elsevier Science Ltd.
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 Published by Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.reprotox.2019.05.058
• Title of Journal or Parent Work: Reproductive Toxicology
• Volume: 87
• Start Page: 70
• End Page: 78
• Grant/Funding Information: This project has been funded in part by the California Breast Cancer Research Program 21UB-8002 (Cohn), and supported by the National Institutes of Health through the HERCULES exposome research center (P30ES019776), S10OD18006 (Jones), U2COD026485 (Jones) and U01OD026489 (Li).
• Keywords: Toxicology; Polyfluoroalkyl substances; National health; Cancer; EtFOSAA; Science & Technology; in utero; DDT Exposure; Nutrition; CHDS; Reproductive Biology; High-resolution metabolomics; Transition; metabolomics; breast cancer; Life Sciences & Biomedicine; Cytotoxicity; Arginine; PFOS; Perfluorooctanoic acid
• Research Categories: Health Sciences, Toxicology; Health Sciences, Obstetrics and Gynecology; Health Sciences, Public Health

Abstract

High-resolution metabolomics (HRM) profiling of metabolic fingerprints can improve understanding of how poly and perfluoroalkyl substances (PFASs) induce metabolic alterations of in utero environment and impact fetal health. HRM profiling and quantification of PFASs were performed for 397 maternal perinatal serum samples collected from 1959-1967 in the Child Health and Development Studies (CHDS). We used Metabolome-Wide Association Studies (MWAS) and pathway enrichment analysis for metabolic associations with PFOS, its precursor EtFOSAA, and EtFOSAA-to-PFOS ratio. Distinct metabolic profiles were found with EtFOSAA and PFOS. Urea cycle metabolites such as arginine, lysine and creatine had opposite associations with EtFOSAA (negative) and PFOS (positive); whereas, carnitine shuttle metabolites were found to be exclusively and positively associated with PFOS indicating perturbation in fatty acid metabolism. These differential metabolic associations for precursor and end-product represent an important first step in identifying how PFASs alter the in utero environment and potentially leads to disease risk.