Infection by Virulent Brucella Species Impairs Human Extravillous Trophoblast Function: Implications for Placental Pathogenesis

Brucella infections are associated with gestational complications in both humans and animals, including spontaneous abortion, premature delivery, and infertility. Successful pregnancy requires the proper invasion and functional integrity of extravillous trophoblasts (EVTs), specialized fetal cells that remodel the maternal decidua. However, the direct impact of the major human-pathogenic species on human EVT biology remains incompletely characterized. Here, we investigated in vitro the effects of B. abortus, B. melitensis, and B. suis infections on the fitness of a human EVT cell line (Swan71). Infection with all three species induced a proinflammatory profile in EVT, with increased CXCL8, CCL2 and IL-6 production. Infection markedly impaired EVT migration (wound closure) and reduced EVT invasive capacity in a matrix invasion assay. EVT tubulogenesis was affected by the infection, with all the species reducing master segments and B. suis and B. melitensis additionally reducing master junctions and meshes. Blastocyst-like spheroids derived from infected EVTs showed reduced outgrowth on decidualized endometrial cell monolayers, with B. suis exhibiting the most consistent effect. Antiproliferative effects were observed at 24 h for B. abortus and B. suis and at 48 h for B. melitensis, preceding marked cell death (late apoptotic features became pronounced only at 72 h post-infection). Collectively, our findings demonstrate that major human-pathogenic Brucella species induce an early dysfunctional state in human EVTs, affecting cellular processes involved in implantation and placental vascular remodeling.