Thyroid disrupting effects of perfluoroundecanoic acid and perfluorotridecanoic acid in zebrafish (Danio rerio) and rat pituitary (GH3) cell line

Abstract

Due to global restriction on perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), the use of long-chain perfluoroalkyl substances (PFASs, C > 8) and their environmental occurrences have increased. PFOS and PFOA have been known for thyroid disruption, however, knowledge is still limited on thyroid disrupting effects of long-chain PFASs (C > 10). In this study, two long-chain perfluorinated carboxylic acids (PFCAs), i.e., perfluoroundecanoic acid (PFUnDA) and perfluorotridecanoic acid (PFTrDA), were chosen and investigated for thyroid disrupting effects, using zebrafish embryo/larvae and rat pituitary cell line (GH3). For comparison, PFOA was also added as a test chemical and also investigated for its thyroid disruption potential. Following a 5 d exposure to PFTrDA, zebrafish larvae showed upregulation of the genes responsible for thyroid hormone synthesis (tshβ, nkx2.1, nis, tpo, mct8) and (de)activation (dio1, dio2). In contrast, both PFUnDA and PFOA induced no regulatory changes except for upregulation of a thyroid metabolism related gene (ugt1ab). Morphological changes such as decreased eyeball size, increased yolk sac size, or deflated swim bladder, occurred following exposure to PFUnDA, PFTrDA, and PFOA. In GH3 cells, exposure to PFUnDA and PFTrDA upregulated Tshβ gene, suggesting that these PFCAs increase thyroid hormone synthesis through stimulation by Tsh. In summary, both long-chain PFCAs could cause transcriptional changes of thyroid regulating genes that may lead to increased malformation of the zebrafish larvae, but the pathway of thyroid disruption appears to be different by the chain length. Confirmation and validation in adult fish following long term exposure are warranted.