Micro/nanoplastics induce thyroid follicular cell pyroptosis to trigger thyrotoxicity by activating NF-κB signaling

Micro/nanoplastics (MNP) have emerged as ubiquitous environmental contaminants with demonstrated bioaccumulation potential in organisms through multiple exposure pathways, posing substantial health risks globally. While mounting evidence indicates that MNP exposure adversely affects various organ systems including the nervous, reproductive, and digestive systems, the specific mechanisms underlying MNP-induced thyrotoxicity remain enigmatic. 4-week-old male C57BL/6 mice were administered microplastics (MP, 5 μm) or nanoplastics (NP, 50 nm) via intragastric gavage at 30 mg/kg for 4 and 8 weeks. The thyroid architecture and endocrine function were evaluated by histological staining and thyroid hormones ELISA kit. The expression of apoptosis indicators (BCL2, BAX, CASPASE3), inflammatory factors (IL-1β, IL-18, TNF-α) and pyroptosis related-proteins (NLRP3, CASPASE1 and GSDMD), as well as the activity of NF-κB signaling were determined by immunofluorescence. We found that MNP exposure induces significant thyrotoxicity characterized by disrupted thyroid follicular architecture, comprised endocrine function, heightened apoptosis, and excessive inflammatory cytokines production, with NP exhibiting a more pronounced effect than MP. Mechanistically, MNP exposure stimulated thyroid follicular cell pyroptosis by upregulation of key pyroptotic mediators including NLRP3, CASPASE1, and GSDMD, driven by NF-κB signaling pathway activation. Collectively, these findings provide novel mechanistic insights into MNP-induced thyroid toxicity and highlight the critical role of follicular cell pyroptosis, contributing to our understanding of the adverse health consequences associated with environmental plastic pollution.