Alpha-Fe₂O₃ elicits diameter-dependent effects during exposure to an in vitro model of the human placenta

Iron oxide nanoparticles offer unique possibilities due to the change in their physico-chemical parameters when synthesized on the nanoscale (10 ^-9 m) compared to their bulk forms. While novel uses exist for these materials when synthesized as nanoparticles, their unintended effects on the human body and specifically during pregnancy remain ill defined. In this study, an iron oxide nanoparticle, α-Fe₂O₃, was employed and the potential toxicity due to exposure was assessed in the widely used model human placental cell line BeWo b30. These cells were grown as epithelia, and subsequently assessed for their epithelial integrity, reactive oxygen species production and cellular viability, ultrastructural and morphological disruption, and genotoxicity as a result of exposure to α-Fe₂O₃ nanoparticles. Transepithelial electrical resistance indicated that exposure to the large (50 and 78 nm), but not small (15 nm) diameter particles of α-Fe₂O₃ nanomaterial resulted in leakiness of the epithelium. Exposure to the large diameters of 50 and 78 nm resulted in increases in cell death and reactive oxygen species. Disruption of junctional integrity as monitored by immunolocalization of the tight junction protein ZO-1 was found to occur as a consequence of exposure to large diameter NPs. It was found that there was reduction in the number of microvilli responsible for increased surface area for nutrient absorption after exposing the epithelia to large diameter NPs. Finally, genotoxicity as assessed by DNA microarray and confirmed by QPCR indicated that the large diameter particles (78 nm) induce apoptosis in these cells. These data indicate that large (50 and 78 nm), but not small (15 nm) α-Fe₂O₃ nanoparticles disrupt the barrier function of this epithelium as assessed by in vitro analysis.