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

Familari, Mary LU ; Nääv, Åsa LU ; Erlandsson, Lena LU ; de Iongh, Robb U.; Isaxon, Christina LU ; Strandberg, Bo LU ; Lundh, Thomas LU ; Hansson, Stefan R. LU and Malmqvist, Ebba LU (2019) In PLoS ONE 14(7).
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;... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
14
issue
7
publisher
Public Library of Science
external identifiers
  • scopus:85069660242
ISSN
1932-6203
DOI
10.1371/journal.pone.0218799
language
English
LU publication?
yes
id
6a1ca940-74b0-4937-81cf-12bf1f3b1a34
date added to LUP
2019-08-23 11:46:11
date last changed
2019-09-19 14:01:39
@article{6a1ca940-74b0-4937-81cf-12bf1f3b1a34,
  abstract     = {<p>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.</p>},
  articleno    = {e0218799},
  author       = {Familari, Mary and Nääv, Åsa and Erlandsson, Lena and de Iongh, Robb U. and Isaxon, Christina and Strandberg, Bo and Lundh, Thomas and Hansson, Stefan R. and Malmqvist, Ebba},
  issn         = {1932-6203},
  language     = {eng},
  month        = {07},
  number       = {7},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Exposure of trophoblast cells to fine particulate matter air pollution leads to growth inhibition, inflammation and ER stress},
  url          = {http://dx.doi.org/10.1371/journal.pone.0218799},
  volume       = {14},
  year         = {2019},
}