Impact of Deoxynivalenol, Cytokines, and Particulate Matter on Human Trophoblast Cells

Placental inflammation and dysfunction play critical roles in adverse pregnancy outcomes, including preeclampsia and intrauterine growth restriction. Exposure to environmental factors, such as dietary toxins, infectious agents, and pollution, is thought to increase the risk of these outcomes. Despite the widespread use of HTR-8/SVneo and BeWo cells as trophoblast models, their comparative sensitivity to maternal exposome-related stimuli has not been systematically evaluated within the same experimental framework. we examined the responses of HTR-8/SVneo and BeWo trophoblast cell lines to mycotoxin deoxynivalenol (DON), an inflammatory cytokine cocktail (CC; TNF-α, IL-1β, IFN-γ), and particulate matter (PM2.5). Cells were seeded with either 0.2% or 1% penicillin/streptomycin (P/S) and exposed for 24 h. Cytokine secretion (IL-6 and IL-8), human chorionic gonadotropin (hCG) production, and mRNA and protein expression of junctional markers (ZO-1, OCLD, CLDN-3, CLDN-4, E-CAD) were analysed. DON significantly increased IL-6 secretion in both cell lines and elevated IL-8 levels in HTR-8/SVneo cells only. DON suppressed hCG production in both cell lines. CC exposure markedly elevated IL-6 and IL-8 levels, particularly in HTR-8/SVneo cells, without affecting hCG level. PM exposure did not significantly alter IL-6, IL-8, or hCG levels in either cell line. DON and CC altered the mRNA and protein expression of junctional markers in BeWo cells(ZO-1, OCLD, CLDN-3,CLDN-4), whereas HTR-8/SVneo cells showed more limited changes. Most cellular responses were consistent across both P/S concentrations. HTR-8/SVneo and BeWo cells exhibit differential sensitivity to DON, CC, and PM2.5, underscoring the importance of cell model selection in in vitro placental toxicology research. These results provide a comparative framework for interpreting trophoblast responses to maternal exposome-related stimuli and highlight the need for functional validation in future studies.