Exposure of trophoblast cells to fine particulate matter air pollution leads to growth inhibition, inflammation and ER stress

Abstract

Ambient air pollution is considered a major environmental health threat to pregnant women. Our previous work has shown an association between exposure to airborne particulate matter (PM) and an increased risk of developing pre-eclamspia. It is now recognized that many pregnancy complications are due to underlying placental dysfunction, and this tissue plays a pivotal role in pre-eclamspia. Recent studies have shown that PM can enter the circulation and reach the human placenta but the effects of PM on human placental function are still largely unknown. In this work we investigated the effects of airborne PM on trophoblast cells. Human, first trimester trophoblast cells (HTR-8/SV) were exposed to urban pollution particles (Malmö PM2.5; Prague PM10) for up to seven days in vitro and were analysed for uptake, levels of hCGβ and IL-6 secretion and proteomic analysis. HTR-8/SVneo cells rapidly endocytose PM within 30 min of exposure and particles accumulate in the cell in perinuclear vesicles. High doses of Prague and Malmö PM (500–5000 ng/ml) significantly decreased hCGβ secretion and increased IL-6 secretion after 48 h exposure. Exposure to PM (50 ng/ml) for 48h or seven days led to reduced cellular growth and altered protein expression. The differentially expressed proteins are involved in networks that regulate cellular processes such as inflammation, endoplasmic reticulum stress, cellular survival and molecular transport pathways. Our studies suggest that trophoblast cells exposed to low levels of urban PM respond with reduced growth, oxidative stress, inflammation and endoplasmic reticulum stress after taking up the particles by endocytosis. Many of the dysfunctional cellular processes ascribed to the differentially expressed proteins in this study, are similar to those described in PE, suggesting that low levels of urban PM may disrupt cellular processes in trophoblast cells. Many of the differentially expressed proteins identified in this study are involved in inflammation and may be potential biomarkers for PE.

Urban PM2.5 Induces Cellular Toxicity, Hormone Dysregulation, Oxidative Damage, Inflammation, and Mitochondrial Interference in the HRT8 Trophoblast Cell Line

“…In this study, the molecular effects of PM2.5 on first trimester trophoblast cells were evaluated by studying mechanisms related to cytotoxicity, cellular disruption, mitochondrial function, inflammatory response, and hormone production. We have previously conducted a study of the effects of PM2.5 on trophoblast cells showing a reduction in cellular growth, endoplasmic reticulum stress, and altered protein expression (43). In this study, we confirm our previous results as well as broaden the scope to include additional organelle systems.…”

“…Experimental studies have established an association between exposure to PM2.5 containing high levels of metals or PAH and increased ROS production in the exposed cells (62). Correspondingly, our previous and current results illustrate that trophoblast cells absorb PAHs and, thereafter, exhibit an altered production of ROS (43). Considering that ROS is a major driver of the progression of PE, through systemic inflammation and vascular endothelial damage, these results are unexpected and allude to the complexity of PM2.5's impact on biological systems.…”

“…Levels up to 5,000 ng/ml, for example, could correspond to 25 µg/m 3 , which is the WHO target for short term exposure (24 h), and 10,000 ng/ml might correspond to levels in a more polluted city with PM2.5 concentrations of 50 µg/m 3 . Previous studies have estimated the physiological range to be similar to the doses used in this study (43).…”

Immunobiology of Acute Chorioamnionitis

“…In particular, we review how inflammation is propagated in different tissue compartments at the maternal-fetal interface, the role of resident cells interacting with immune cells at the interface, the role of inflammatory mediators, and how host-microbe interactions affect pathology. Although sterile inflammation (3,4), environmental pollutants (5)(6)(7), cigarette smoke (8,9), and other toxicants play an important role in the pathogenesis of IUI, these considerations are beyond the scope of this review.…”

Prolonged Exposure to Traffic-related Particulate Matter Showed Distinct Molecular Mechanisms of Lung Injury in Rats

“…Mass spectrometry (MS)-based proteomics analysis that enables unbiased identi cation and quanti cation of thousands of proteins has been applied to study the aberrant molecular pro les upon PM-induced damages on primary skin keratinocytes (11), trophoblast cells (12), lung epithelial cells (13), rat lung (14) and rat brain (15). Several dysregulated proteins involved in mitochondria dysfunction, energy metabolism and ER stress were discovered as potential biomarkers for PM-induced organ damage.…”