Fine particulate matter exposure induces cell cycle arrest and inhibits migration and invasion of human extravillous trophoblast, as determined by an iTRAQ-based quantitative proteomics strategy

摘要

Highlights ? Quantitative proteomic analysis of difference protein in HTR-8/SVneo cells exposed to PM 2.5 . ? PM 2.5 induces DNA damage and cell cycle G2/M arrest in HTR-8/SVneo cells. ? PM 2.5 may induce the failure of placenta implantation by decreasing the migration and invasion ability of HTR-8/SVneo cells. Abstract Long-term exposure to fine particulate matter (PM2.5) may cause adverse pregnancy outcomes but the mechanisms are not clear. Our research confirms that PM2.5 induced DNA damage, and inhibited cell proliferation in HTR-8/SVneo cells, presenting in a dose- and time-dependent manners. Using quantitative proteomics, the 182 and 486 differentially expressed proteins in cells treated with 120μgml ?1 PM2.5 for 24 and 48h were involved in many critical biological processes, including of cell proliferation, response to DNA damage, regulation of small GTPase mediated signal transduction, and etc. Further validation indicated that PM2.5 blocked the cell cycle at the G2/M phase through activation of the ATR-Cyclin E1/Cdk6 pathway, and it reduced the migration and invasion by upregulating TIMP1 and TIMP2 expression and downregulating Collagen I expression. Our findings were consistent with the observed effects of PM2.5 on cell cycle arrest and inhibition of migration and invasion in human extravillous trophoblast.