Effects of prenatal pyrethroid exposure on placental transcriptomes in a Northern Thailand agricultural cohort study Público
Holstein, Jacqueline (Spring 2023)
Abstract
Background: Prenatal pyrethroid exposure has been linked to adverse postnatal neurodevelopmental outcomes. Animal models have found that the disruption of dopamine expression in the placenta may be linked to postnatal behavioral characteristics of neurobehavioral disorders such as ADHD, autism, and neuromotor conditions.
Objective Our goal was to assess the placental transcriptome to examine the hypothesis that dopamine biomarkers, specifically D5, D1, D2, dopamine active transporter (DAT), Tyrosine hydroxylase (TH), Calmodulin-dependent Protein Kinase IIa (CAMK2A), monoamine oxidase A (MAOA), voltage-gated sodium channel type Ia (VSSC), catechol O-methyltransferase (COMT), and vesicular monoamine transporter (VMAT) are associated with pyrethroid exposure and postnatal neurodevelopmental scales in the Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE) cohort.
Methods: This study is making use of existing data from the SAWASDEE cohort. For pyrethroid exposure models a composite score of log-transformed 3-phenoxybenzoic acid (3-PBA) across all trimesters was used. At 4 months after birth, nurses certified in use of the NICU Network Neurobehavioral Scale (NNNS) captured neurobehavioral outcomes. For 254 participants, we profiled the term placental transcriptome using RNA-Seq. Generalized linear models were used to examine the association between average 3-PBA across trimester and the transcriptome; overall and stratified by infant sex, and between eight neurobehavioral scales and the transcriptome. Differentially expressed genes were subjected to gene ontology enrichment analysis as well as ConsensusPathDB over-representation.
Results: No hypothesized dopaminergic pathway genes met FDR threshold (<0.05) for differential expression with pyrethroid exposure. When looking at the pyrethroid models stratified by infant sex we did observe two genes that were differentially expressed in males: IGKC and KRT24. After performing pathway analysis on NNNS data we found that similar to previous animal research; metabolism of RNA, ETC: OXPHOS system in mitochondria, Oxidative phosphorylation, Respiratory electron transport, and mRNA Splicing pathways were all significantly expressed.
Conclusion: Our study findings suggest that exposure to pyrethroid during pregnancy may disrupt placental gene networks. Gene network disruption may lead to down-stream changes in placental function and ultimately affect the developing fetus.
Table of Contents
Introduction…………………………………………………………………………….……….1
Methods………………………………………………………………………………………....3
Study Population…………………………………………………………………….…..3
Urine Samples……………………………………………………………………….…..4
NNNS………………………………………………………………………………..…...4
RNA sequencing………………………………………………………………………...5
Statistical analysis……………………………………………………………………....5
Results………………………………………………………………………………….……….6
Pyrethroid Metabolites……………………………………………………………….…6
NNNS Data………………………………………………………..……………………..9
Discussion………………………………………………………………………………….....11
Pyrethroid………………………………………………………………...…………….11
NNNS Data…………………………………………………………………………..…12
Limitations………………………………………………………………………………12
Conclusion………………………………………………………………………………….....13
Figures…………………...…………………………………………………………………….14
Figure 1. ………………………………………………………………………………..14
Figure 2. ………………………………………………………………………………..15
References…………………………………………………………………………………….16
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