Assessment on metabolic perturbations associated with maternal exposure to phthalates among pregnant African American women 公开
Zhang, Xiaoyue (Spring 2021)
Abstract
Background: Phthalates have been linked with numerous harmful health effects. Limited data are available on the molecular mechanism underlying phthalate toxicity on human health. In this analysis, we measured urinary phthalate metabolites and conducted high-resolution metabolomics (HRM) to identify biological perturbations associated with phthalate exposures among pregnant African American (AA) women, who are disproportionately exposed to high phthalates levels.
Methods: We used untargeted HRM profiling to characterize serum samples collected during early (8-14 weeks gestation) and late (24-30 weeks gestation) pregnancy from 73 participants from the Atlanta AA Maternal-Child cohort. We measured 8 urinary phthalate metabolites in early and late pregnancy, including Monoethyl phthalate (MEP), Mono-n-butyl phthalate (MBP), Mono(2-ethlyhexyl) phthalate (MEHP), and Mono (2-ethyl-5-hydroxyhexyl phthalate (MEHHP), to assess maternal exposures to phthalates. Metabolite and metabolic pathway perturbation were evaluated using an untargeted HRM workflow.
Results: Geometric mean creatinine-adjusted levels of urinary MEP, MBP, MEHP, and MEHHP were 67.3, 6.6, 1.4, and 4.1 μg/g creatinine, respectively, with MEP and MEHP higher than the mean levels of Non-Hispanic blacks in the general US population (2015-2016). There were 814 and 1,435 metabolic features significantly associated with at least one phthalate metabolites during early and late pregnancy, respectively. Metabolic pathway enrichment analysis revealed perturbations in four inflammation- and oxidative stress-related pathways associated with phthalate metabolite levels during both early and late pregnancy, including glycerophospholipid, urea cycle, arginine, and tyrosine metabolism. We confirmed 10 metabolites associated with urinary phthalates, including thyroxine and thiamine, which were negatively associated with MEP, as well as tyramine and phenethylamine, which were positively associated with MEHP and MEHHP.
Conclusion: Our results demonstrate that urinary phthalate levels are associated with perturbations in biological pathways connected with inflammation and oxidative stress. The findings support future hypothesis-testing investigations on potential molecular mechanisms underlying the impact of maternal phthalates exposure on adverse health outcomes.
Table of Contents
Introduction ............................................................................................................................................................ 1
Methods ...................................................................................................................................................................2
Study participants .................................................................................................................................................... 2
Phthalate exposure assessments in maternal urine samples ......................................................................................... 3
High-resolution metabolomics profiling..................................................................................................................... 4
Untargeted metabolome-wide association study (MWAS) ............................................................................................ 4
Metabolic pathway enrichment analysis .................................................................................................................... 5
Chemical annotation and metabolite confirmation ..................................................................................................... 6
Results .................................................................................................................................................................... 6
Maternal urinary phthalate metabolites..................................................................................................................... 6
Association of phthalate exposure and metabolic profiles in participants ..................................................................... 7
Perturbated metabolic pathways associated with phthalate exposure .......................................................................... 8
Chemical annotation and confirmation on metabolic features significantly associated with phthalate exposure ..............8
Discussion .............................................................................................................................................................. 9
Conclusion ............................................................................................................................................................ 13 Reference............................................................................................................................................................... 14
Tables ................................................................................................................................................................... 18
Figures .................................................................................................................................................................. 21
About this Master's Thesis
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