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. 2023 May 1:224:115490.
doi: 10.1016/j.envres.2023.115490. Epub 2023 Feb 23.

Associations between prenatal organophosphate pesticide exposure and placental gene networks

Qian Li  1 , Corina Lesseur  1 , Pranathi Srirangam  2 , Kirtan Kaur  1 , Karen Hermetz  3 , W Michael Caudle  3 , Nancy Fiedler  4 , Parinya Panuwet  3 , Tippawan Prapamontol  5 , Warangkana Naksen  6 , Panrapee Suttiwan  7 , Brittney O Baumert  8 , Ke Hao  1 , Dana Boyd Barr  3 , Carmen J Marsit  3 , Jia Chen  9
Affiliations

Associations between prenatal organophosphate pesticide exposure and placental gene networks

Qian Li et al. Environ Res. .

Abstract

Background: Exposure to organophosphate (OP) pesticides during pregnancy has been linked to deficiencies of neurobehavioral development in childhood; however, the molecular mechanisms underlying this association remain elusive. The placenta plays a crucial role in protecting the fetus from environmental insults and safeguarding proper fetal development including neurodevelopment. The aim of our study is to evaluate changes in the placental transcriptome associated with prenatal OP exposure.

Methods: Pregnant farm workers from two agricultural districts in northern Thailand were recruited for the Study of Asian Women and Offspring's Development and Environmental Exposures (SAWASDEE) from 2017 to 2019. For 254 participants, we measured maternal urinary concentrations of six nonspecific dialkyl phosphates (DAP) metabolites in early, middle, and late pregnancy. In parallel, we profiled the term placental transcriptome from the same participants using RNA-Sequencing and performed Weighted Gene co-expression Network Analysis (WGCNA). Generalized linear regression modeling was used to examine associations of urinary OP metabolites and placental co-expression module eigenvalues.

Results: We identified 21 gene co-expression modules in the placenta. From the six DAP metabolites assayed, diethylphosphate (DEP) and diethylthiophosphate (DETP) were detected in more than 70% of the urine samples. Significant associations between DEP at multiple time points and two specific placental gene modules were observed. The 'black' module, enriched in genes involved in epithelial-to-mesenchymal transition (EMT) and hypoxia, was negatively associated with DEP in early (p = 0.034), and late pregnancies (p = 0.016). The 'lightgreen' module, enriched in genes involved in myogenesis and EMT, was negatively associated with DEP in late pregnancy (p = 0.010). We observed 2 hub genes (CELSR1 and PYCR1) of the 'black' module to be negatively associated with DEP in early and late pregnancies.

Conclusions: Our results suggest that prenatal OP exposure may disrupt placental gene networks in a time-dependent manner. Such transcriptomic effects may lead to down-stream changes in placental function that ultimately affect the developing fetus.

Keywords: Birth cohort; Gene networks; Organophosphates; Placenta; Transcriptome.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1.
Figure 1.
Gene expression modules detected by WGCNA. Numbers and length of the bar reflect the sizes of corresponding modules. Selected Hallmark Enrichment categories for each module are shown.
Figure 2.
Figure 2.
Expression of hub genes (one dot corresponds to one sample) among the different levels of DEP metabolite.
See this image and copyright information in PMC

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