The Effects of Polystyrene Nanoplastic and Bisphenol A Exposure on the Thyroid Gland in Mice.

The health risks associated with exposure to polystyrene nanoplastics (PS-NPs) and bisphenol A (BPA) are a recognized global concern, yet their individual and combined toxic effects on the mammalian thyroid remain poorly defined. This integrated in vivo and in vitro study demonstrates that in mice, four-week exposure to PS-NPs alone induced dose-dependent thyroid hormone disruption and structural damage, while co-exposure with BPA resulted in clearly exacerbated injury, indicating an additive toxic interaction. This additive effect was characterized by markedly worsened histopathology and a distinct shift in the thyroid transcriptome from pathways such as cytoplasmic translation toward extracellular matrix (ECM) organization and collagen fibril assembly. Mechanistically, although each pollutant downregulated core circadian genes (Per3 and Dbp), co-exposure did not produce further suppression. Instead, in vivo analysis revealed that PS-NPs enhanced BPA's inhibitory effect on specific ECM-related genes (Col1a2, Col5a1 and Col5a2). Notably, this transcriptional synergy was not observed in human thyroid cells in vitro, where co-exposure failed to amplify BPA's inhibitory action. These findings indicate that the additive thyroid toxicity is not driven by amplification of shared intracellular stress pathways in thyrocytes, but more likely stems from complex tissue-level interactions, with dysregulation of the extracellular matrix playing a central role. Overall, our results reveal an additive effect between PS-NPs and BPA and underscore the environmental risks posed by the co-occurrence of emerging pollutants and nanoparticles.