School of BioSciences, University of Melbourne, Parkville, Australia.
Lund University, Faculty of Medicine, Department of Clinical Sciences, Division of Obstetrics and Gynecology, Lund, Sweden.
PLoS One. 2019 Jul 18;14(7):e0218799. doi: 10.1371/journal.pone.0218799. eCollection 2019.
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.
大气污染被认为是对孕妇的主要环境健康威胁。我们之前的工作表明，暴露于空气中的颗粒物（PM）与子痫前期风险增加之间存在关联。现在人们认识到，许多妊娠并发症是由于胎盘功能障碍引起的，而这种组织在子痫前期中起着关键作用。最近的研究表明，PM 可以进入循环并到达人胎盘，但 PM 对人胎盘功能的影响在很大程度上仍不清楚。在这项工作中，我们研究了空气中的 PM 对滋养层细胞的影响。将人早孕滋养层细胞（HTR-8/SV）在体外暴露于城市污染颗粒（马尔默 PM2.5；布拉格 PM10）长达七天，并分析摄取、hCGβ 水平和 IL-6 分泌以及蛋白质组学分析。HTR-8/SVneo 细胞在暴露后 30 分钟内迅速内吞 PM，颗粒在核周囊泡中积累。高剂量的布拉格和马尔默 PM（500-5000ng/ml）在暴露 48 小时后显著降低 hCGβ 分泌并增加 IL-6 分泌。暴露于 PM（50ng/ml）48 小时或七天导致细胞生长减少和蛋白表达改变。差异表达的蛋白参与调节细胞过程的网络，如炎症、内质网应激、细胞存活和分子运输途径。我们的研究表明，暴露于低水平城市 PM 的滋养层细胞通过内吞作用摄取颗粒后，细胞生长减少，氧化应激、炎症和内质网应激。在这项研究中，差异表达的蛋白所描述的许多功能障碍的细胞过程与 PE 相似，这表明低水平的城市 PM 可能会破坏滋养层细胞的细胞过程。在这项研究中鉴定的许多差异表达蛋白都参与炎症，可能是 PE 的潜在生物标志物。
