Maternal Exposure to Diesel Exhaust Particles (DEPs) During Pregnancy and Adverse Pregnancy Outcomes: Focusing on the Effect of Particulate Matter on Trophoblast, Epithelial-Mesenchymal Transition

Abstract

During pregnancy, exposure to fine particulate matter (PM2.5), particularly diesel exhaust particles (DEPs), elevates the risk of placental dysfunction-related pregnancy complications; however, the underlying cellular mechanisms have yet to be fully elucidated. The objective of this study was to assess the effects of PM2.5 exposure on trophoblast functions and their interaction with endometrial stromal cells. We utilized a three-dimensional (3D) model in which human first-trimester trophoblasts (Sw71) formed blastocyst-like spheroids and were cultured with human endometrial stromal cells (HESCs). Trophoblast proliferation, migration, invasion, and 3D network formation following DEP exposure (0.5-20 mu g/mL) were assessed using methyl thiazolyl diphenyl-tetrazolium bromide (MTT), wound healing, migration, and invasion assays. The expression levels of genes related to the epithelial-mesenchymal transition (EMT) were quantified by real-time reverse-transcription quantitative polymerase chain reaction (RT-qPCR). DEP exposure significantly inhibited trophoblast proliferation, migration, and invasion. DEP treatment dysregulated the EMT program by significantly decreasing the expression of key mesenchymal markers (SNAI1, SNAI2, SOX2, and KLF4) while upregulating epithelial markers. These changes may be related to inhibited trophoblast migration toward HESC monolayers and 3D invasive network formation. DEP directly impairs critical trophoblast functions that are essential for successful pregnancy. Disruption of the EMT program represents a molecular mechanism by which traffic-related air pollution contributes to placental dysfunction and pregnancy complications, highlighting the significant reproductive risks posed by ambient air pollution.