Global metabolomic alterations associated with endocrine-disrupting chemicals among pregnant individuals and newborns

Jagadeesh Puvvula; Lucie C Song; Klaudia J Zalewska; Ariel Alexander; Kathrine E Manz; Joseph M Braun; Kurt D Pennell; Emily A DeFranco; Shuk-Mei Ho; Yuet-Kin Leung; Shouxiong Huang; Ann M Vuong; Stephani S Kim; Zana Percy; Priyanka Bhashyam; Raymund Lee; Dean P Jones; Vilinh Tran; Dasom V Kim; Antonia M Calafat; Julianne C Botelho; Aimin Chen

doi:10.1007/s11306-024-02219-7

Global metabolomic alterations associated with endocrine-disrupting chemicals among pregnant individuals and newborns

Metabolomics. 2025 Jan 25;21(1):20. doi: 10.1007/s11306-024-02219-7.

Authors

Jagadeesh Puvvula¹, Lucie C Song², Klaudia J Zalewska³, Ariel Alexander⁴, Kathrine E Manz⁵, Joseph M Braun⁶, Kurt D Pennell⁷, Emily A DeFranco⁸, Shuk-Mei Ho⁹, Yuet-Kin Leung⁹, Shouxiong Huang¹⁰, Ann M Vuong¹¹, Stephani S Kim¹², Zana Percy¹³, Priyanka Bhashyam², Raymund Lee², Dean P Jones¹⁴, Vilinh Tran¹⁴, Dasom V Kim¹⁵, Antonia M Calafat¹⁶, Julianne C Botelho¹⁶, Aimin Chen¹⁷

Affiliations

¹ Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Jagadeesh.Puvvula@pennmedicine.upenn.edu.
² College of Arts & Sciences, University of Pennsylvania, Philadelphia, PA, USA.
³ College of Nursing, University of Pennsylvania, Philadelphia, PA, USA.
⁴ Carleton College, Northfield, MN, USA.
⁵ Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
⁶ Department of Epidemiology, Brown University, Providence, RI, USA.
⁷ School of Engineering, Brown University, Providence, RI, USA.
⁸ Department of Obstetrics and Gynecology, College of Medicine, University of Kentucky, Lexington, KY, USA.
⁹ Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
¹⁰ Pathogen-Host Interaction Program, Texas Biomedical Research Institute, San Antonio, TX, USA.
¹¹ Department of Epidemiology and Biostatistics, School of Public Health, University of Nevada Las Vegas, Las Vegas, NV, USA.
¹² Health Research, Battelle Memorial Institute, Columbus, OH, USA.
¹³ Department of Environmental & Public Health Sciences, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
¹⁴ Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, GA, USA.
¹⁵ Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹⁶ National Center for Environmental Health, U.S. Centers for Disease Control and Prevention, Atlanta, GA, USA.
¹⁷ Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Abstract

Background: Gestational exposure to non-persistent endocrine-disrupting chemicals (EDCs) may be associated with adverse pregnancy outcomes. While many EDCs affect the endocrine system, their effects on endocrine-related metabolic pathways remain unclear. This study aims to explore the global metabolome changes associated with EDC biomarkers at delivery.

Methods: This study included 75 pregnant individuals who delivered at the University of Cincinnati Hospital from 2014 to 2017. We measured maternal urinary biomarkers of paraben/phenol (12), phthalate (13), and phthalate replacements (4) from the samples collected during the delivery visit. Global serum metabolome profiles were analyzed from maternal blood (n = 72) and newborn (n = 63) cord blood samples collected at delivery. Fifteen of the 29 urinary biomarkers were excluded due to low detection frequency or potential exposures during hospital stay. We assessed metabolome-wide associations between 14 maternal urinary biomarkers and maternal/newborn metabolome profiles. Additionally, performed enrichment analysis to identify potential alterations in metabolic pathways.

Results: We observed metabolome-wide associations between maternal urinary concentrations of phthalate metabolites (mono-isobutyl phthalate), phthalate replacements (mono-2-ethyl-5-carboxypentyl terephthalate, mono-2-ethyl-5-hydroxyhexyl terephthalate) and phenols (bisphenol-A, bisphenol-S) and maternal serum metabolome, using q-value < 0.2 as a threshold. Additionally, associations of phthalate metabolites (mono-n-butyl phthalate, monobenzyl phthalate) and phenols (2,5-dichlorophenol, BPA) with the newborn metabolome were noted. Enrichment analyses revealed associations (p-gamma < 0.05) with amino acid, carbohydrate, lipid, glycan, vitamin, and other cofactor metabolism pathways.

Conclusion: Maternal paraben, phenol, phthalate, and phthalate replacement biomarker concentrations at delivery were associated with maternal and newborn serum global metabolome.

Keywords: Fetus; Metabolome; Phenol; Phthalate; Pregnancy; Untargeted metabolomics.

MeSH terms

Adult
Biomarkers* / blood
Biomarkers* / urine
Endocrine Disruptors* / blood
Endocrine Disruptors* / urine
Female
Fetal Blood / chemistry
Fetal Blood / metabolism
Humans
Infant, Newborn
Maternal Exposure / adverse effects
Metabolome*
Metabolomics* / methods
Phthalic Acids* / metabolism
Phthalic Acids* / urine
Pregnancy
Young Adult

Substances

Endocrine Disruptors
Phthalic Acids
Biomarkers

Abstract

MeSH terms

Substances

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