TY - JOUR
T1 - Metabolome-wide association study of the relationship between chlorpyrifos exposure and first trimester serum metabolite levels in pregnant Thai farmworkers
AU - for the SAWASDEE birth cohort investigative team
AU - Liang, Donghai
AU - Batross, Jonathan
AU - Fiedler, Nancy
AU - Prapamontol, Tippawan
AU - Suttiwan, Panrapee
AU - Panuwet, Parinya
AU - Naksen, Warangkana
AU - Baumert, Brittney O.
AU - Yakimavets, Volha
AU - Tan, Youran
AU - D'Souza, Priya
AU - Mangklabruks, Ampica
AU - Sittiwang, Supattra
AU - Kaewthit, Kristsanachai
AU - Kohsuwan, Kanyapak
AU - Promkam, Nattawadee
AU - Pingwong, Sureewan
AU - Ryan, P. Barry
AU - Barr, Dana Boyd
AU - Steenland, Kyle
AU - Smarr, Melissa M.
AU - Lee, Grace
AU - Yakimavets, Olya
AU - Hawkins, Tamaria
AU - Sullivan, Margaret
AU - Ohman-Strickland, Pamela
AU - Robson, Mark
AU - Iamsupasit, Sompoch
AU - Siriwong, Wattasit
AU - Barr, Kathryn J.
AU - Greenwald, Rachel
AU - Cheatham, Carol
AU - Mangklapuark, Ampica
AU - Kerdnoi, Tanyaporn
AU - Srirak, Namtip
AU - Hongsibsong, Surat
AU - Dokjunyam, Chayada
AU - Nimmapirat, Pimjuta
AU - Promduang, Wathoosiri
AU - Jayakittivaraloes, Natabhol
AU - Kunsupa, Kewalin
AU - Kantasri, Anchana
AU - Kaewthit, Kritsanachai
AU - Wongkampaun, Anchalee
AU - Thongjan, Nathaporn
AU - Dawandee, Ranuka
AU - Chaimidchid, Maytinee
AU - Soonsawat, Sasiwimon
AU - Sritongkom, Kingpaka
AU - Namakunna, Sakawrat
N1 - Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/12
Y1 - 2022/12
N2 - Introduction: Organophosphate (OP) insecticides, including chlorpyrifos, have been linked with numerous harmful health effects on maternal and child health. Limited data are available on the biological mechanisms and endogenous pathways underlying the toxicity of chlorpyrifos exposures on pregnancy and birth outcomes. In this study, we measured a urinary chlorpyrifos metabolite and used high-resolution metabolomics (HRM) to identify biological perturbations associated with chlorpyrifos exposure among pregnant women in Thailand, who are disparately exposed to high levels of OP insecticides. Methods: This study included 50 participants from the Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE). We used liquid chromatography-high resolution mass spectrometry to conduct metabolic profiling on first trimester serum samples collected from participants to evaluate metabolic perturbations in relation to chlorpyrifos exposures. We measured 3,5,6-trichloro-2-pyridinol (TCPy), a specific metabolite of chlorpyrifos and chlorpyrifos-methyl, in first trimester urine samples to assess the levels of exposures. Following an untargeted metabolome-wide association study workflow, we used generalized linear models, pathway enrichment analyses, and chemical annotation to identify significant metabolites and pathways associated with urinary TCPy levels. Results: In the 50 SAWASDEE participants, the median urinary TCPy level was 4.36 μg TCPy/g creatinine. In total, 691 unique metabolic features were found significantly associated with TCPy levels (p < 0.05) after controlling for confounding factors. Pathway analysis of metabolic features associated with TCPy indicated perturbations in 24 metabolic pathways, most closely linked to the production of reactive oxygen species and cellular damage. These pathways include tryptophan metabolism, fatty acid oxidation and peroxisome metabolism, cytochromes P450 metabolism, glutathione metabolism, and vitamin B3 metabolism. We confirmed the chemical identities of 25 metabolites associated with TCPy levels, including glutathione, cystine, arachidic acid, itaconate, and nicotinamide adenine dinucleotide. Discussion: The metabolic perturbations associated with TCPy levels were related to oxidative stress, cellular damage and repair, and systemic inflammation, which could ultimately contribute to health outcomes, including neurodevelopmental deficits in the child. These findings support the future development of sensitive biomarkers to investigate the metabolic underpinnings related to pesticide exposure during pregnancy and to understand its link to adverse outcomes in children.
AB - Introduction: Organophosphate (OP) insecticides, including chlorpyrifos, have been linked with numerous harmful health effects on maternal and child health. Limited data are available on the biological mechanisms and endogenous pathways underlying the toxicity of chlorpyrifos exposures on pregnancy and birth outcomes. In this study, we measured a urinary chlorpyrifos metabolite and used high-resolution metabolomics (HRM) to identify biological perturbations associated with chlorpyrifos exposure among pregnant women in Thailand, who are disparately exposed to high levels of OP insecticides. Methods: This study included 50 participants from the Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE). We used liquid chromatography-high resolution mass spectrometry to conduct metabolic profiling on first trimester serum samples collected from participants to evaluate metabolic perturbations in relation to chlorpyrifos exposures. We measured 3,5,6-trichloro-2-pyridinol (TCPy), a specific metabolite of chlorpyrifos and chlorpyrifos-methyl, in first trimester urine samples to assess the levels of exposures. Following an untargeted metabolome-wide association study workflow, we used generalized linear models, pathway enrichment analyses, and chemical annotation to identify significant metabolites and pathways associated with urinary TCPy levels. Results: In the 50 SAWASDEE participants, the median urinary TCPy level was 4.36 μg TCPy/g creatinine. In total, 691 unique metabolic features were found significantly associated with TCPy levels (p < 0.05) after controlling for confounding factors. Pathway analysis of metabolic features associated with TCPy indicated perturbations in 24 metabolic pathways, most closely linked to the production of reactive oxygen species and cellular damage. These pathways include tryptophan metabolism, fatty acid oxidation and peroxisome metabolism, cytochromes P450 metabolism, glutathione metabolism, and vitamin B3 metabolism. We confirmed the chemical identities of 25 metabolites associated with TCPy levels, including glutathione, cystine, arachidic acid, itaconate, and nicotinamide adenine dinucleotide. Discussion: The metabolic perturbations associated with TCPy levels were related to oxidative stress, cellular damage and repair, and systemic inflammation, which could ultimately contribute to health outcomes, including neurodevelopmental deficits in the child. These findings support the future development of sensitive biomarkers to investigate the metabolic underpinnings related to pesticide exposure during pregnancy and to understand its link to adverse outcomes in children.
KW - Biomarkers
KW - Birth cohort
KW - Farmworker
KW - Metabolomics
KW - Organophosphate
KW - Thailand
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UR - http://www.scopus.com/inward/citedby.url?scp=85138607322&partnerID=8YFLogxK
U2 - 10.1016/j.envres.2022.114319
DO - 10.1016/j.envres.2022.114319
M3 - Article
C2 - 36108722
AN - SCOPUS:85138607322
SN - 0013-9351
VL - 215
JO - Environmental research
JF - Environmental research
M1 - 114319
ER -