Effect of particulate matter 2.5 on gene expression profile and cell signaling in JEG‐3 human placenta cells

Abstract

Particulate matter the environmental toxicant, with a diameter less than or equal to 2.5 μm (PM ) is a common cause of several respiratory diseases. In recent years, several studies have suggested that PM can influence diverse diseases, such as respiratory diseases, cardiovascular diseases, metabolic diseases, dementia, and female reproductive disorders, and unhealthy birth outcomes. In addition, several epidemiological studies have reported that adverse health effects of PM can differ depending on regional variations. In the present study, to evaluate specific adverse health effects of PM , we collected two different PM samples from an underground parking lot and ambient air, and we evaluated cytotoxicity with eight different cell lines originating from human organs. Then, we selected JEG-3 human placenta cells, which show high cytotoxicity to both PM samples. Through RNA sequencing, gene expression profiling, and a gene ontology (GO) analysis of JEG-3 after exposure to two different PM samples, we identified 1021 commonly expressed genes involved in immune responses, the regulation of apoptosis, and so forth, which are known to induce several adverse health effects. In addition, we identified genes related to the calcium-signaling pathway, steroid hormone biosynthesis, and the cytokine-cytokine receptor interaction through a Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then, we confirmed these gene expressions using qRT-PCR, and the protein levels of mitogen-activated protein kinases and COX-2 with progesterone decreased using western blotting and enzyme-linked immunosorbent assay. In conclusion, this study suggests the possible toxic mechanism of human placenta that might be associated with PM -induced female reproductive disorders.

Prenatal exposure to particulate matter and placental gene expression

“…While the purpose of examining the two cohorts separately was in anticipation of replication of findings, inconsistency in findings may have resulted from differences (including demographic differences) in the study populations as well as variation in PM 2.5 exposure (such as source, composition, and magnitude) between the cohorts. PM 2.5 is a complex mixture of particles and its composition, which varies depending on seasons and regions, may lead to different outcomes, including gene expression ( Kim et al, 2018 ; Bell et al, 2007 ; Honkova et al, 2018 ). While the overall size of the study is large, study power may still preclude identification of significant differences in expression of some genes, particularly in the GAPPS study.…”

“…DNA adduct and DNA methylation) include signatures of DNA damage as well as genomic, epigenomic, proteomic, metabolomics and exposomic changes that occur in placenta following exposure to ambient air pollution and are closely related to placental function ( Luyten et al, 2018 ). While investigations of placental gene expression can further our understanding of placental functions that are affected by air pollution and related gene-environment interactions, few epidemiological and basic science studies have been conducted on PM 2.5 exposure and placental gene expression ( Luyten et al, 2018 ; Saenen et al, 2015 ; Whyatt et al, 1995 ; Kingsley et al, 2017 ; Kim et al, 2018 ; Deyssenroth et al, 2021 ). Findings from these studies indicated that exposure to PM 2.5 particles, which are small and can get deep into the lung and bloodstream, is associated with changes in placental expression of brain-derived neurotrophic factor ( BDNF ) ( Saenen et al, 2015 ), synapsin 1 ( SYN1 ) ( Saenen et al, 2015 ), cytochrome P450 1A1 ( CYP1A1 ) ( Whyatt et al, 1995 ), imprinted genes ( Kingsley et al, 2017 ), and genes related to amino acid transport and cellular respiration ( Deyssenroth et al., 2021 ).…”

Transcriptomics and Other Omics Approaches to Investigate Effects of Xenobiotics on the Placenta

“…We will consider the evidence to date that air pollution disrupts the placental transcriptome and methylome profiles. Culturing of JEG-3 human placental cells in the presence of such PM affected genes involved in immune response, apoptosis regulation, calcium signaling pathway, steroid hormone biosynthesis, and cytokine-cytokine receptor interaction (Kim et al, 2018). Protein levels for mitogen activated protein kinases (MAPK) and COX2 were reduced in the PM 2 .…”

Pollution and endometriosis: A deep dive into the environmental impacts on women's health

“…Activation of pro-inflammatory signalling pathways, such as nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, has been implicated. 96 PM2.5 exposure can generate reactive oxygen species (ROS), leading to oxidative stress in cells. 97 Oxidative stress-related pathways, such as the Nrf2 (nuclear factor erythroid 2-related factor 2) pathway, may be activated in response to PM2.5.…”

“…PM2.5 exposure can lead to inflammation through various mechanisms. Activation of pro‐inflammatory signalling pathways, such as nuclear factor‐kappa B (NF‐κB) and mitogen‐activated protein kinase (MAPK) pathways, has been implicated 96 . PM2.5 exposure can generate reactive oxygen species (ROS), leading to oxidative stress in cells 97 .…”