TY - JOUR
T1 - Global metabolomic alterations associated with endocrine-disrupting chemicals among pregnant individuals and newborns
AU - Puvvula, Jagadeesh
AU - Song, Lucie C.
AU - Zalewska, Klaudia J.
AU - Alexander, Ariel
AU - Manz, Kathrine E.
AU - Braun, Joseph M.
AU - Pennell, Kurt D.
AU - DeFranco, Emily A.
AU - Ho, Shuk Mei
AU - Leung, Yuet Kin
AU - Huang, Shouxiong
AU - Vuong, Ann M.
AU - Kim, Stephani S.
AU - Percy, Zana
AU - Bhashyam, Priyanka
AU - Lee, Raymund
AU - Jones, Dean P.
AU - Tran, Vilinh
AU - Kim, Dasom V.
AU - Calafat, Antonia M.
AU - Botelho, Julianne C.
AU - Chen, Aimin
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/2
Y1 - 2025/2
N2 - 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.
AB - 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.
KW - Fetus
KW - Metabolome
KW - Phenol
KW - Phthalate
KW - Pregnancy
KW - Untargeted metabolomics
UR - http://www.scopus.com/inward/record.url?scp=85216998308&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85216998308&partnerID=8YFLogxK
U2 - 10.1007/s11306-024-02219-7
DO - 10.1007/s11306-024-02219-7
M3 - Article
C2 - 39863779
AN - SCOPUS:85216998308
SN - 1573-3882
VL - 21
JO - Metabolomics
JF - Metabolomics
IS - 1
M1 - 20
ER -
