Metabolome-Wide Association Study of the Relationship Between Insecticide Exposure and First Trimester Serum Metabolite Levels in North Thailand Women Open Access

Batross, Jonathan (Spring 2021)

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Intro: Organophosphate (OP) insecticides are a common group of neurotoxic insecticides. Their main target is acetylcholinesterase which are in charge of muscle contractions. While OP insecticides are made to kill pests and insects, they can also affect humans. Thailand is a country highly dependent on agricultural work and thus has a high usage of OP insecticides. Women who are pregnant frequently work in these fields, and thus can expose the fetus to these insecticides, ultimately causing neurodevelopmental issues among the newborns and children.

Methods: This study is a subset of the Study of Asian Women and Offspring’s Development and Environmental Exposures (SAWASDEE) study which followed 322 women-child pairs from pregnancy until three years old. We used high-resolution metabolomics (HRM) to assess serum samples collected on 50 of these women at the first trimester. To assess the levels of OP insecticide exposure, we measured the stable metabolite 3,5,6-trichloro-2-pyridinol (TCPY) in urine samples. Following an untargeted metabolome-wide association study (MWAS) workflow, we used liquid chromatography-mass spectroscopy (LCMS) instruments to conduct metabolic profiling on our samples, and then we used in house bioinformatics software in Python and R to identify significant metabolites and pathways associated with OP exposures. We used 2 multiple linear regression models which included recruitment site, age, ethnicity, if their husband smoked, the use of medication, and use of fertilizer and pesticides. One model also controlled for creatinine adjust TCPY levels.

Results: We found 37 significant pathways that occurred in at least 2 of our models. Most of these metabolic pathways were linked to the production of reactive oxygen species (ROS) which indicates cellular damage. These pathways include: Tryptophan metabolism, fatty acid oxidation and peroxisome metabolism, drug metabolism using CYP450, Glutathione metabolism, and Vitamin B3.

Discussion: This work is meant to pioneer and further add research of the maternal metabolome during pregnancy and OP insecticide exposure. This research is especially important because this exposure is occurring when the fetus is most at risk of neural development disruption. It can also lead to targeted interventions which would lower the health burden for this large population.

Table of Contents

Introduction ..........1

Methods ...............2

Results .................8

Discussion ...........10

Conclusion ..........15

References ..........15

Figures & Tables .22

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