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Urinary Paraben Concentrations and Associations with the Periconceptional Urinary Metabolome: Untargeted and Targeted Metabolomics Analyses of Participants from the Early Pregnancy Study

BACKGROUND: Parabens, found in everyday items from personal care products to foods, are chemicals with endocrine-disrupting activity, which has been shown to influence reproductive function. OBJECTIVES: This study investigated whether urinary concentrations of methylparaben, propylparaben, or butylp...

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Autores principales: Rosen Vollmar, Ana K., Rattray, Nicholas J.W., Cai, Yuping, Jain, Abhishek, Yan, Hong, Deziel, Nicole C., Calafat, Antonia M., Wilcox, Allen J., Jukic, Anne Marie Z., Johnson, Caroline H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Environmental Health Perspectives 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10498870/
https://www.ncbi.nlm.nih.gov/pubmed/37702489
http://dx.doi.org/10.1289/EHP12125
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author Rosen Vollmar, Ana K.
Rattray, Nicholas J.W.
Cai, Yuping
Jain, Abhishek
Yan, Hong
Deziel, Nicole C.
Calafat, Antonia M.
Wilcox, Allen J.
Jukic, Anne Marie Z.
Johnson, Caroline H.
author_facet Rosen Vollmar, Ana K.
Rattray, Nicholas J.W.
Cai, Yuping
Jain, Abhishek
Yan, Hong
Deziel, Nicole C.
Calafat, Antonia M.
Wilcox, Allen J.
Jukic, Anne Marie Z.
Johnson, Caroline H.
author_sort Rosen Vollmar, Ana K.
collection PubMed
description BACKGROUND: Parabens, found in everyday items from personal care products to foods, are chemicals with endocrine-disrupting activity, which has been shown to influence reproductive function. OBJECTIVES: This study investigated whether urinary concentrations of methylparaben, propylparaben, or butylparaben were associated with the urinary metabolome during the periconceptional period, a critical window for female reproductive function. Changes to the periconceptional urinary metabolome could provide insights into the mechanisms by which parabens could impact fertility. METHODS: Urinary paraben concentrations were measured in paired pre- and postconception urine samples from 42 participants in the Early Pregnancy Study, a prospective cohort of 221 women attempting to conceive. We performed untargeted and targeted metabolomics analyses using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry. We used principal component analysis, orthogonal partial least-squares discriminant analysis, and permutation testing, coupled with univariate statistical analyses, to find metabolites associated with paraben concentration at the two time points. Potential confounders were identified with a directed acyclic graph and used to adjust results with multivariable linear regression. Metabolites were identified using fragmentation data. RESULTS: Seven metabolites were associated with paraben concentration (variable importance to projection score [Formula: see text] , false discovery rate–corrected [Formula: see text]). We identified four diet-related metabolites to the Metabolomics Standards Initiative (MSI) certainty of identification level 2, including metabolites from smoke flavoring, grapes, and olive oil. One metabolite was identified to the class level only (MSI level 3). Two metabolites were unidentified (MSI level 4). After adjustment, three metabolites remained associated with methylparaben and propylparaben, two of which were diet-related. No metabolomic markers of endocrine disruption were associated with paraben concentrations. DISCUSSION: This study identified novel relationships between urinary paraben concentrations and diet-related metabolites but not with metabolites on endocrine-disrupting pathways, as hypothesized. It demonstrates the feasibility of integrating untargeted metabolomics data with environmental exposure information and epidemiological adjustment for confounders. The findings underscore a potentially important connection between diet and paraben exposure, with applications to nutritional epidemiology and dietary exposure assessment. https://doi.org/10.1289/EHP12125
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spelling pubmed-104988702023-09-14 Urinary Paraben Concentrations and Associations with the Periconceptional Urinary Metabolome: Untargeted and Targeted Metabolomics Analyses of Participants from the Early Pregnancy Study Rosen Vollmar, Ana K. Rattray, Nicholas J.W. Cai, Yuping Jain, Abhishek Yan, Hong Deziel, Nicole C. Calafat, Antonia M. Wilcox, Allen J. Jukic, Anne Marie Z. Johnson, Caroline H. Environ Health Perspect Research BACKGROUND: Parabens, found in everyday items from personal care products to foods, are chemicals with endocrine-disrupting activity, which has been shown to influence reproductive function. OBJECTIVES: This study investigated whether urinary concentrations of methylparaben, propylparaben, or butylparaben were associated with the urinary metabolome during the periconceptional period, a critical window for female reproductive function. Changes to the periconceptional urinary metabolome could provide insights into the mechanisms by which parabens could impact fertility. METHODS: Urinary paraben concentrations were measured in paired pre- and postconception urine samples from 42 participants in the Early Pregnancy Study, a prospective cohort of 221 women attempting to conceive. We performed untargeted and targeted metabolomics analyses using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry. We used principal component analysis, orthogonal partial least-squares discriminant analysis, and permutation testing, coupled with univariate statistical analyses, to find metabolites associated with paraben concentration at the two time points. Potential confounders were identified with a directed acyclic graph and used to adjust results with multivariable linear regression. Metabolites were identified using fragmentation data. RESULTS: Seven metabolites were associated with paraben concentration (variable importance to projection score [Formula: see text] , false discovery rate–corrected [Formula: see text]). We identified four diet-related metabolites to the Metabolomics Standards Initiative (MSI) certainty of identification level 2, including metabolites from smoke flavoring, grapes, and olive oil. One metabolite was identified to the class level only (MSI level 3). Two metabolites were unidentified (MSI level 4). After adjustment, three metabolites remained associated with methylparaben and propylparaben, two of which were diet-related. No metabolomic markers of endocrine disruption were associated with paraben concentrations. DISCUSSION: This study identified novel relationships between urinary paraben concentrations and diet-related metabolites but not with metabolites on endocrine-disrupting pathways, as hypothesized. It demonstrates the feasibility of integrating untargeted metabolomics data with environmental exposure information and epidemiological adjustment for confounders. The findings underscore a potentially important connection between diet and paraben exposure, with applications to nutritional epidemiology and dietary exposure assessment. https://doi.org/10.1289/EHP12125 Environmental Health Perspectives 2023-09-13 /pmc/articles/PMC10498870/ /pubmed/37702489 http://dx.doi.org/10.1289/EHP12125 Text en https://ehp.niehs.nih.gov/about-ehp/licenseEHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted.
spellingShingle Research
Rosen Vollmar, Ana K.
Rattray, Nicholas J.W.
Cai, Yuping
Jain, Abhishek
Yan, Hong
Deziel, Nicole C.
Calafat, Antonia M.
Wilcox, Allen J.
Jukic, Anne Marie Z.
Johnson, Caroline H.
Urinary Paraben Concentrations and Associations with the Periconceptional Urinary Metabolome: Untargeted and Targeted Metabolomics Analyses of Participants from the Early Pregnancy Study
title Urinary Paraben Concentrations and Associations with the Periconceptional Urinary Metabolome: Untargeted and Targeted Metabolomics Analyses of Participants from the Early Pregnancy Study
title_full Urinary Paraben Concentrations and Associations with the Periconceptional Urinary Metabolome: Untargeted and Targeted Metabolomics Analyses of Participants from the Early Pregnancy Study
title_fullStr Urinary Paraben Concentrations and Associations with the Periconceptional Urinary Metabolome: Untargeted and Targeted Metabolomics Analyses of Participants from the Early Pregnancy Study
title_full_unstemmed Urinary Paraben Concentrations and Associations with the Periconceptional Urinary Metabolome: Untargeted and Targeted Metabolomics Analyses of Participants from the Early Pregnancy Study
title_short Urinary Paraben Concentrations and Associations with the Periconceptional Urinary Metabolome: Untargeted and Targeted Metabolomics Analyses of Participants from the Early Pregnancy Study
title_sort urinary paraben concentrations and associations with the periconceptional urinary metabolome: untargeted and targeted metabolomics analyses of participants from the early pregnancy study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10498870/
https://www.ncbi.nlm.nih.gov/pubmed/37702489
http://dx.doi.org/10.1289/EHP12125
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