Extracellular vesicles and their miRNA contents counterbalance the pro-inflammatory effect of air pollution during physiological pregnancy: A focus on Syncytin-1 positive vesicles. (November 2022)

• Record Type: Journal Article
• Authors: Ferrari, Luca; Iodice, Simona; Cantone, Laura; Solazzo, Giulia; Dioni, Laura; Hoxha, Mirjam; Vicenzi, Marco; Mozzoni, Paola; Bergamaschi, Enrico; Persico, Nicola; Bollati, Valentina
• Is Part Of: Environment international. Volume 169(2022)
• Publication Date: 2022-11
• Subjects: Particulate matter -- Extracellular vesicles -- Pregnancy; ADM adrenomedullin -- AGT angiotensinogen -- AmpScore amplification score -- APLN apelin -- ARPA Lombardy Regional Environmental Protection Agency Lombardy -- BMI body mass index -- CI confidence interval -- CRH corticotropin-Releasing Hormone -- CT cycle threshold -- EDN1 endothelin 1 -- EDTA ethylenediaminetetraacetic acid -- EV extracellular vesicles -- EV-miRNA EV miRNA content -- FLT1 fms Related Receptor Tyrosine Kinase 1 -- HLA-G human leukocyte antigen G -- IL10 interleukin 10 -- IL6 Interleukin 6 -- IQR interquartile range -- LCI lower confidence interval -- LEP leptin -- miRNA microRNAs -- NTA nanoparticle tracking analysis -- PBS phosphate-buffered saline -- PGF placental growth factor -- PM particulate matter -- PM10 PM with aerodynamic diameters of ≤ 2.5 µm -- PM2.5 PM with aerodynamic diameters of ≤ 10 µm -- Q1 first quartile -- Q3 third quartile -- qFDR False Discovery Rate -- RQ relative quantification -- RT-qPCR Real-time quantitative PCR -- SD standard deviation -- SE standard error -- SERPIN1 serpin1 -- sICAM-1 soluble intercellular adhesion molecule-1 -- sVCAM-1 circulating vascular cell adhesion molecule-1 -- Sync-1 Syncitin-1 -- Treg regulatory T lymphocytes -- UCI upper confidence interval -- VEGFA vascular endothelial growth factor A -- Δ% percentage change; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2022.107502
• Languages: English
• ISSNs: 0160-4120

Abstract

Highlights: Short-term PM10 and PM2.5 exposures were associated with increased concentrations of plasmatic EVs. Increased Sync-1 + EV levels were associated with the plasmatic decrease of the circulating endothelial dysfunction biomarker sVCAM-1. The EV-miRNA dysregulated in response to both PM10 and PM2.5 exposures exhibited putative roles in inflammation, gestational hypertension, and pre-eclampsia. Abstract: The impact of exposure to respirable particulate matter (PM) during pregnancy is a growing concern, as several studies have associated increased risks of adverse pregnancy and birth outcomes, and impaired intrauterine growth with air pollution. The molecular mechanisms responsible for such effects are still under debate. Extracellular vesicles (EVs), which travel in body fluids and transfer microRNAs (miRNAs) between tissues (e.g., pulmonary environment and placenta), might play an important role in PM-induced risk. We sought to determine whether the levels of PM with aerodynamic diameters of ≤10 µm (PM10 ) and ≤2.5 µm (PM2.5 ) are associated with changes in plasmatic EV release and EV-miRNA content by investigating 518 women enrolled in the INSIDE study during the first trimester of pregnancy. In all models, we included both the 90-day averages of PM (long-term effects) and the differences between the daily estimate of PM and the 90-day average (short-term effects). Short-term PM10 and PM2.5 were associated with increased concentrations of all seven EV types that we assayed (positive for human antigen leukocyte G (HLA-G), Syncytin-1 (Sync-1), CD14, CD105, CD62e, CD61, or CD25 determinants), while long-term PM10 showed a trend towards decreased EV concentrations. Increased Sync-1 + EV levels were associated with the plasmatic decrease of sVCAM-1, but not of sICAM-1, which are circulating biomarkers of endothelial dysfunction. Thirteen EV-miRNAs were downregulated in response to long-term PM10 and PM2.5 variations, while seven were upregulated (p-value < 0.05, false discovery rate p-value (qFDR) < 0.1). Only one EV-miRNA (hsa-miR-221-3p) was downregulated after short-term variations. The identified PM-modulated EV-miRNAs exhibited putative roles in inflammation, gestational hypertension, and pre-eclampsia, as highlighted by miRNA target analysis. Our findings strongly support the hypothesis that EVs have an important role in modulating PM exposure effects during pregnancy, possibly through their miRNA cargo.