# PFAS Alter Thyroid Histology and Cellular Signaling In Vitro and In Vivo

**Authors:** Heather A Hartmann, Kailey P Caroland, Goran W Tumbic, Jessica Rampy, Hua-Chang Chen, Sheau-Chiann Chen, Clara Mannes, Claudia C Wahoski, Matthew A Loberg, Cynthia Liang, Diana Diaz, Megan L Tigue, Quanhu Sheng, Fei Ye, Ethan Lee, Vivian L Weiss

PMC · DOI: 10.1210/jendso/bvaf210 · Journal of the Endocrine Society · 2025-12-18

## TL;DR

This study shows that PFAS chemicals can change thyroid structure and signaling in mice, potentially increasing thyroid disease risk.

## Contribution

The study demonstrates PFAS-induced thyroid histological and signaling changes using an in vivo model and RNA sequencing.

## Key findings

- PFAS exposure altered thyroid architecture and cell structure in mice.
- RNA-sequencing revealed dysregulated gene expression and signaling pathways in PFAS-treated mice.

## Abstract

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.

## Linked entities

- **Chemicals:** PFOS (PubChem CID 74483), PFOA (PubChem CID 9554), GenX (PubChem CID 114481)
- **Diseases:** thyroid cancer (MONDO:0002108)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Diseases:** thyroid cancer (MESH:D013964), thyroid disease (MESH:D013959), cancer (MESH:D009369), toxicity (MESH:D064420)
- **Chemicals:** PFOA (MESH:C023036), GenX (-)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12838522/full.md

## References

71 references — full list in the complete paper: https://tomesphere.com/paper/PMC12838522/full.md

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Source: https://tomesphere.com/paper/PMC12838522