PFAS Alter Thyroid Histology and Cellular Signaling <i>In Vitro</i> and <i>In Vivo</i>

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are toxicants of emerging concern due to their abundance in the environment and potential adverse health effects. PFAS are used in waterproof clothing, makeup, carpets, upholstery, cookware, and fast-food containers. Due to their universal use, they are found globally in the water supply. In fact, these organic pollutants have been found in the blood of 98% of Americans and have been linked to disruption in thyroid hormone biosynthesis and availability. Moreover, several studies have shown that cancer patients may have an increase in PFAS levels and that PFAS exposure increases thyroid cancer risk. Demonstration of concrete PFAS-mediated alterations in thyroid histology and function could have far-reaching implications. To understand the effects of PFAS on thyroid histology, we used a PFAS feeding model with a combination of 3 PFAS compounds (PFOS, PFOA, and GenX) vs control. Mice receiving PFAS treatment showed altered thyroid architecture and cell structure following PFAS exposure. RNA-sequencing data revealed several alterations in gene expression and multiple signaling pathways were dysregulated. Understanding the role of PFAS-mediated toxicity in the thyroid is critically important for the prevention of thyroid disease in the general population.