Use of high-resolution metabolomics to assess the biological perturbations associated with maternal exposure to Bisphenol A and Bisphenol F among pregnant African American women

Background: Human and animal exposure to bisphenol A (BPA) has been associated with adverse developmental and reproductive effects. The molecular mechanisms by which BPA exposure exerts its effects are not well-understood, even less known about its analogues bisphenol F (BPF). To address these knowl...

Full description

Bibliographic Details
Main Authors: Rachel Tchen, Youran Tan, Dana Boyd Barr, P. Barry Ryan, ViLinh Tran, Zhenjiang Li, Yi-Juan Hu, Alicia K. Smith, Dean P. Jones, Anne L. Dunlop, Donghai Liang
Format: Article
Language:English
Published: Elsevier 2022-11-01
Series:Environment International
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0160412022004573
_version_ 1828106907692302336
author Rachel Tchen
Youran Tan
Dana Boyd Barr
P. Barry Ryan
ViLinh Tran
Zhenjiang Li
Yi-Juan Hu
Alicia K. Smith
Dean P. Jones
Anne L. Dunlop
Donghai Liang
author_facet Rachel Tchen
Youran Tan
Dana Boyd Barr
P. Barry Ryan
ViLinh Tran
Zhenjiang Li
Yi-Juan Hu
Alicia K. Smith
Dean P. Jones
Anne L. Dunlop
Donghai Liang
author_sort Rachel Tchen
collection DOAJ
description Background: Human and animal exposure to bisphenol A (BPA) has been associated with adverse developmental and reproductive effects. The molecular mechanisms by which BPA exposure exerts its effects are not well-understood, even less known about its analogues bisphenol F (BPF). To address these knowledge gaps, we conducted an untargeted metabolome-wide association study (MWAS) to identify metabolic perturbations associated with BPA/BPF exposures in a pregnant African American cohort. Methods: From a subset of study participants enrolled in the Atlanta African American Maternal-Child cohort, we collected both urine samples, for targeted exposure assessment of BPA (N = 230) and BPF (N = 48), and serum samples, for high-resolution metabolomics (HRM) profiling (N = 230), during early pregnancy (8–14 weeks’ gestation). Using an established untargeted HRM workflow consisting of MWAS modeling, pathway enrichment analysis, and chemical annotation and confirmation, we investigated the potential metabolic pathways and features associated with BPA/BPF exposures. Results: The geometric mean creatinine-adjusted concentrations of urinary BPA and BPF were 0.85 ± 2.58 and 0.70 ± 4.71 µg/g creatinine, respectively. After false positive discovery rate correction at 20 % level, 264 and 733 unique metabolic features were significantly associated with urinary BPA and BPF concentrations, representing 10 and 12 metabolic pathways, respectively. Three metabolic pathways, including steroid hormones biosynthesis, lysine and lipoate metabolism, were significantly associated with both BPA and BPF exposure. Using chemical standards, we have confirmed the chemical identity of 16 metabolites significantly associated with BPA or BPF exposure. Conclusions: Our findings support that exposure to BPA and BPF in pregnant women is associated with the perturbation of aromatic amino acid metabolism, xenobiotics metabolism, steroid biosynthesis, and other amino acid metabolism closely linked to stress responses, inflammation, neural development, reproduction, and weight regulation.
first_indexed 2024-04-11T10:24:13Z
format Article
id doaj.art-c23452518b6641239b477e801bae76b9
institution Directory Open Access Journal
issn 0160-4120
language English
last_indexed 2024-04-11T10:24:13Z
publishDate 2022-11-01
publisher Elsevier
record_format Article
series Environment International
spelling doaj.art-c23452518b6641239b477e801bae76b92022-12-22T04:29:40ZengElsevierEnvironment International0160-41202022-11-01169107530Use of high-resolution metabolomics to assess the biological perturbations associated with maternal exposure to Bisphenol A and Bisphenol F among pregnant African American womenRachel Tchen0Youran Tan1Dana Boyd Barr2P. Barry Ryan3ViLinh Tran4Zhenjiang Li5Yi-Juan Hu6Alicia K. Smith7Dean P. Jones8Anne L. Dunlop9Donghai Liang10Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USAGangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USAGangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USAGangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USAClinical Biomarkers Laboratory, Division of Pulmonary, Allergy and Critical Care Medicine, School of Medicine, Emory University, Atlanta, GA, USAGangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USADepartment of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USADepartment of Gynecology and Obstetrics, School of Medicine, Emory University, Atlanta, GA, USADepartment of Medicine, School of Medicine, Emory University, Atlanta, GA, USADepartment of Gynecology and Obstetrics, School of Medicine, Emory University, Atlanta, GA, USAGangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA; Corresponding author at: 1518 Clifton Rd, Atlanta, GA 30322, USA.Background: Human and animal exposure to bisphenol A (BPA) has been associated with adverse developmental and reproductive effects. The molecular mechanisms by which BPA exposure exerts its effects are not well-understood, even less known about its analogues bisphenol F (BPF). To address these knowledge gaps, we conducted an untargeted metabolome-wide association study (MWAS) to identify metabolic perturbations associated with BPA/BPF exposures in a pregnant African American cohort. Methods: From a subset of study participants enrolled in the Atlanta African American Maternal-Child cohort, we collected both urine samples, for targeted exposure assessment of BPA (N = 230) and BPF (N = 48), and serum samples, for high-resolution metabolomics (HRM) profiling (N = 230), during early pregnancy (8–14 weeks’ gestation). Using an established untargeted HRM workflow consisting of MWAS modeling, pathway enrichment analysis, and chemical annotation and confirmation, we investigated the potential metabolic pathways and features associated with BPA/BPF exposures. Results: The geometric mean creatinine-adjusted concentrations of urinary BPA and BPF were 0.85 ± 2.58 and 0.70 ± 4.71 µg/g creatinine, respectively. After false positive discovery rate correction at 20 % level, 264 and 733 unique metabolic features were significantly associated with urinary BPA and BPF concentrations, representing 10 and 12 metabolic pathways, respectively. Three metabolic pathways, including steroid hormones biosynthesis, lysine and lipoate metabolism, were significantly associated with both BPA and BPF exposure. Using chemical standards, we have confirmed the chemical identity of 16 metabolites significantly associated with BPA or BPF exposure. Conclusions: Our findings support that exposure to BPA and BPF in pregnant women is associated with the perturbation of aromatic amino acid metabolism, xenobiotics metabolism, steroid biosynthesis, and other amino acid metabolism closely linked to stress responses, inflammation, neural development, reproduction, and weight regulation.http://www.sciencedirect.com/science/article/pii/S0160412022004573Bisphenol ABisphenol FUrinary bisphenol metabolitesHigh-resolution metabolomicsMetabolic perturbations
spellingShingle Rachel Tchen
Youran Tan
Dana Boyd Barr
P. Barry Ryan
ViLinh Tran
Zhenjiang Li
Yi-Juan Hu
Alicia K. Smith
Dean P. Jones
Anne L. Dunlop
Donghai Liang
Use of high-resolution metabolomics to assess the biological perturbations associated with maternal exposure to Bisphenol A and Bisphenol F among pregnant African American women
Environment International
Bisphenol A
Bisphenol F
Urinary bisphenol metabolites
High-resolution metabolomics
Metabolic perturbations
title Use of high-resolution metabolomics to assess the biological perturbations associated with maternal exposure to Bisphenol A and Bisphenol F among pregnant African American women
title_full Use of high-resolution metabolomics to assess the biological perturbations associated with maternal exposure to Bisphenol A and Bisphenol F among pregnant African American women
title_fullStr Use of high-resolution metabolomics to assess the biological perturbations associated with maternal exposure to Bisphenol A and Bisphenol F among pregnant African American women
title_full_unstemmed Use of high-resolution metabolomics to assess the biological perturbations associated with maternal exposure to Bisphenol A and Bisphenol F among pregnant African American women
title_short Use of high-resolution metabolomics to assess the biological perturbations associated with maternal exposure to Bisphenol A and Bisphenol F among pregnant African American women
title_sort use of high resolution metabolomics to assess the biological perturbations associated with maternal exposure to bisphenol a and bisphenol f among pregnant african american women
topic Bisphenol A
Bisphenol F
Urinary bisphenol metabolites
High-resolution metabolomics
Metabolic perturbations
url http://www.sciencedirect.com/science/article/pii/S0160412022004573
work_keys_str_mv AT racheltchen useofhighresolutionmetabolomicstoassessthebiologicalperturbationsassociatedwithmaternalexposuretobisphenolaandbisphenolfamongpregnantafricanamericanwomen
AT yourantan useofhighresolutionmetabolomicstoassessthebiologicalperturbationsassociatedwithmaternalexposuretobisphenolaandbisphenolfamongpregnantafricanamericanwomen
AT danaboydbarr useofhighresolutionmetabolomicstoassessthebiologicalperturbationsassociatedwithmaternalexposuretobisphenolaandbisphenolfamongpregnantafricanamericanwomen
AT pbarryryan useofhighresolutionmetabolomicstoassessthebiologicalperturbationsassociatedwithmaternalexposuretobisphenolaandbisphenolfamongpregnantafricanamericanwomen
AT vilinhtran useofhighresolutionmetabolomicstoassessthebiologicalperturbationsassociatedwithmaternalexposuretobisphenolaandbisphenolfamongpregnantafricanamericanwomen
AT zhenjiangli useofhighresolutionmetabolomicstoassessthebiologicalperturbationsassociatedwithmaternalexposuretobisphenolaandbisphenolfamongpregnantafricanamericanwomen
AT yijuanhu useofhighresolutionmetabolomicstoassessthebiologicalperturbationsassociatedwithmaternalexposuretobisphenolaandbisphenolfamongpregnantafricanamericanwomen
AT aliciaksmith useofhighresolutionmetabolomicstoassessthebiologicalperturbationsassociatedwithmaternalexposuretobisphenolaandbisphenolfamongpregnantafricanamericanwomen
AT deanpjones useofhighresolutionmetabolomicstoassessthebiologicalperturbationsassociatedwithmaternalexposuretobisphenolaandbisphenolfamongpregnantafricanamericanwomen
AT anneldunlop useofhighresolutionmetabolomicstoassessthebiologicalperturbationsassociatedwithmaternalexposuretobisphenolaandbisphenolfamongpregnantafricanamericanwomen
AT donghailiang useofhighresolutionmetabolomicstoassessthebiologicalperturbationsassociatedwithmaternalexposuretobisphenolaandbisphenolfamongpregnantafricanamericanwomen