BACKGROUND: In the human placenta, we have detected the MPs by Raman microspectroscopy analysis and, for the first time, with transmission electron microscopy. MPs fragments have been localized in different compartments of placental tissue, free in the cytoplasm and within organelles like lysosomes. Moreover, their presence has been correlated with ultrastructural alterations of some cell organelles, typical of metabolic stress, mainly dilated rough endoplasmic reticulum and numerous swollen electrodense mitochondria, as well as signs derived from involuting organelles. As a result, we have speculated that microplastics in the placenta could be responsible for pathological traits activation such as oxidative stress, apoptosis, and inflammation causing long-term effects on the health of the mother and child. To demonstrate the cytotoxicity of PS-NPs on the placenta and confirm the MATERIALS AND METHODS: HTR8/SVneo cells were treated, for 24 h and 48h, with increasing concentrations (10, 25, 50, 75, and 100 μg/mL) of 0.05 µm polystyrene (PS) and cellular viability was evaluated by Counting Kit-8. Fluorescent PS-NPs examined under fluorescence/confocal microscopy were used to investigate the internalization of plastics in the placenta cells. Transmission electron microscopy was used to evaluate possible PS-NPs-dependent ultrastructural alterations of cells and organelles. RESULTS: Our study shows that starting from 24 h exposure, PS-NPs treatment, at 50 μg/mL dose, has a cytotoxic effect on placental cells, causing the death of 40% of cells and affecting the morphology of the surviving cells. In addition, PS-NPs alter the ultrastructure of some organelles in the surviving cells, like those we have already described CONCLUSION: Based on electron microscopy and immunofluorescence analysis and