Jayabharthi Thirumalazhagan, Shivadas Sivasubramaniam, Vadivel Parthsarathy
Environmental particulate matter pollution is commonly associated with adverse pregnancy outcome, and impaired trophoblast development and function; however, the underlying biological mechanisms remain poorly understood. This meta-analysis aims to investigate the detrimental effects of particulate matter on cell viability, gene and protein expression pathways in trophoblast cells in vitro by systematically searching Google Scholar, PubMed, CENTRAL, Embase, CINAHL, MEDLINE for articles published up to September 2025. Pooled relative risks (RR) with 95% confidence intervals (CIs) were calculated to evaluate the gene and protein expression on exposure to PM2.5. Of 1506 records screened, 12 studies were selected based on the inclusion criteria. Results showed PM2.5 reduces cell viability collectively by 20.68%, disrupts steroidogenic enzymes (CYP11A1, 3β-HSD1, FDXR) separates hCG production from progesterone synthesis, further exacerbating inflammatory signalling. PM2.5 induces oxidative stress that further causes DNA damage, activating ATR-mediated p53-independent apoptosis. Angiogenic signalling through VEGF-VEGFR2-MEK-ERK-mTOR is supressed due to PM2.5 exposure. Matrix remodelling is also impaired due to the dominant TIMP expression, RhoA dysregulation, and Collagen I loss by collectively reducing migration, and invasive capability of the trophoblast cells. Overall, this meta-analysis underscores the underlying mechanisms by which PM2.5 consistently impairs trophoblast function and contributes to placental dysfunction.