Global Metabolomic Alterations Associated with Endocrine-disrupting Chemicals Among Pregnant Individuals and Newborns

Overview

Journal Metabolomics

Publisher Springer

Date 2025 Jan 25

PMID 39863779

Authors

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

Affiliations

Soon will be listed here.

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.

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