| Summary: | Extracellular vesicles released by the primary pathogen of periodontal disease <i>Porphyromonas gingivalis</i> (<i>Pg</i>), referred to as outer membrane vesicles (OMVs), have been associated with the pathogenesis of systemic diseases like cardiovascular disease, rheumatoid arthritis, and Alzheimer’s disease. A pathogenic role for <i>Pg</i> by disrupting placental homeostasis was proposed in the association between periodontal disease and adverse pregnancy outcomes. On the basis that trophoblast-derived factors modulate endothelial and immune cell profiles in normal pregnancy and the scarce presence of <i>Pg</i> in placenta, we hypothesized that OMVs from <i>Pg</i> affect trophoblast cell phenotype, impairing trophoblast–endothelium and trophoblast–neutrophil interactions. By means of in vitro designs with first-trimester human trophoblast cells, endothelial cells, and freshly isolated neutrophils, we showed that <i>Pg</i> OMVs are internalized by trophoblast cells and modulate the activity and expression of functional markers. Trophoblast cells primed with <i>Pg</i> OMVs enhanced neutrophil chemoattraction and lost their anti-inflammatory effect. In addition, reduced migration with enhanced adhesion of monocytes was found in endothelial cells upon incubation with the media from trophoblast cells pretreated with <i>Pg</i> OMVs. Taken together, the results support a pathogenic role of <i>Pg</i> OMVs at early stages of pregnancy and placentation through disruption of trophoblast contribution to vascular transformation and immune homeostasis maintenance.
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