Exposure to polystyrene nanoparticles induce disruption of mitochondrial homeostasis and impairs trophoblast cell invasion and migration via MDM2/ROCK1 pathway

Abstract

Background Polystyrene nanoparticles (PS-NPs) are recognized as environmental pollutants with potential reproductive toxicity. This study delves into the impacts of PS-NPs exposure on trophoblast cells, specifically examining mitochondrial dysfunction, cell invasion and migration. Methods Trophoblast cells were exposed to PS-NPs to evaluate the effects on cell proliferation, apoptosis, mitochondrial function (including mitochondrial membrane potential, intracellular ROS levels, and gene expression), autophagy, inflammatory responses and cell motility. Co-immunoprecipitation and Western blotting analyses were employed to assess the expressions and interactions of MDM2 and ROCK1 under PS-NPs exposure conditions. Results We observed that PS-NPs exposure impaired trophoblast cell proliferation, promoted apoptosis, and disrupted mitochondrial function, evident by ROS elevation, mitochondrial membrane potential reduction, and altered gene expression. Increased autophagy activity and inflammatory cytokine release indicated cellular stress. Moreover, PS-NPs impeded cell migration and invasion, with exacerbated effects upon MDM2 knockdown and ROCK1 inhibition. Conclusion The study elucidates the intricate connections among mitochondrial dysfunction, autophagy, inflammation, and cell motility in response to PS-NPs, suggesting that targeting the MDM2-ROCK1 pathway could offer a promising approach to alleviate PS-NP-induced toxicity in trophoblast cells and support placental health.