Albers K, Ni A, Ramirez B, Ruiz S, Skrehot H, Jonson DE - "Computational Association of PFAS Exposure and Hypothyroidism" Toxicologist 174(1):507 (2020)
https://www.researchgate.net/profile/Da ... 41-507.pdf
".. we were able to define the relationship between PFAS exposure and hypothyroidism, in which PFAS exposure increases DIO3 production, deactivating T3 and T4, therefore inhibiting normal metabolic functions...In terms of individuals who are already immune compromised, such as people with Hashimoto’s Disease, it can be expected that exposure to PFAS would exacerbate their already existing condition of hypothyroidism. This is because PFOS and PFOA trigger an increase of TGFB1 production. This increase in TGFB1 targets our gene of interest, DIO3, causing an increase in DIO3 mRNA and thus an increase in the deactivation of T3 and T4. Having PFOS and PFOA induce a decrease in T3 and T4 levels would exacerbate a situation where T3 and T4 hormone levels are already low."
Birgersson L, Jouve J, Jönsson E, Asker N, Andreasson F, Golovko O, Ahrens L, Sturve J - "Thyroid function and immune status in perch (Perca fluviatilis) from lakes contaminated with PFASs or PCBs" Ecotoxicol Environ Saf 222:112495 (2021)
https://www.sciencedirect.com/science/a ... 1321006072
"Our results showed lower levels of T3 as well as lower amounts of lymphocytes and granulocytes in perch collected from the PFAS-contaminated site compared to reference sites. In addition, expressions of mRNA coding for thyroid hormone metabolising enzymes (dio2 and dio3) and thyroid receptor α (thra) were significantly different in these fish compared to their reference site."
Cassone CG, Vongphachan V, Chiu S, Williams KL, Letcher RJ, Pelletier E, Crump D, Kennedy SW - "In ovo effects of perfluorohexane sulfonate and perfluorohexanoate on pipping success, development, mRNA expression, and thyroid hormone levels in chicken embryos" Toxicol Sci 127(1):216-24 (2012) doi: 10.1093/toxsci/kfs072
https://academic.oup.com/toxsci/article ... 16/1637202
"Type II and type III 5'-deiodinases (D2 and D3) and cytochrome P450 3A37 mRNA levels were induced in liver tissue of chicken embryos exposed to PFHxS, whereas D2, neurogranin (RC3), and octamer motif binding factor 1 mRNA levels were upregulated in cerebral cortex."
Cheng Y, Cui Y, Chen HM, Xie WP - "Thyroid disruption effects of environmental level perfluorooctane sulfonates (PFOS) in Xenopus laevis" Ecotoxicology 20(8):2069-78 (2011)doi: 10.1007/s10646-011-0749-3
https://link.springer.com/article/10.10 ... 011-0749-3
"PFOS exposure resulted in up-regulation of thyroid hormone-regulated genes-thyroid receptor beta A (TRβA), basic transcription element-binding protein (BTEB) and type II deiodinase (DI2) mRNA expression, presented as an inverted U-shaped dose response pattern."
Crute CE, Hall SM, Landon CD, Garner A, Everitt JI, Zhang S, Blake B, Olofsson D, Chen H, Murphy SK, Stapleton HM, Feng L - "Evaluating maternal exposure to an environmental per and polyfluoroalkyl substances (PFAS) mixture during pregnancy: Adverse maternal and fetoplacental effects in a New Zealand White (NZW) rabbit model" Sci Total Environ 838(Pt 4):156499 (2022) doi: 10.1016/j.scitotenv.2022.156499
(Mixture of 10 PFAS: Differences in expression by exposure status did not reach significance, but trends in differential expression of DIO3, MCT8, and SULT1E1 were detected (p<0.2). Interestingly, DIO3, SCARB1, and SULT1A1 showed trending mRNA differences by sex, though none reached statistical significance."
Also: "Importantly, this finding is the first to show a possible link between exposure to an environmentally-relevant PFAS-mixture and hypertension" [see fluoride research].
Dong H, Curran I, Williams A, Bondy G, Yauk CL, Wade MG - "Hepatic miRNA profiles and thyroid hormone homeostasis in rats exposed to dietary potassium perfluorooctanesulfonate (PFOS)" Environ Toxicol Pharmacol 41:201-10 (2016). doi: 10.1016/j.etap.2015.12.009
https://www.sciencedirect.com/science/a ... 8915301514
"Our analysis also revealed transcripts that may mediate PFOS-induced effects on TH homeostasis including: activation of the CAR/PXR pathway, phase II/III enzymes, and deiodinase [D1]. These changes are consistent with low serum TH due to
enhanced metabolic clearance of TH."
Kim S, Stroski KM, Killeen G, Smitherman C, Simcik MF, Brooks BW - "8:8 Perfluoroalkyl phosphinic acid affects neurobehavioral development, thyroid disruption, and DNA methylation in developing zebrafish" Sci Total Environ 736:139600 (2020) doi: 10.1016/j.scitotenv.2020.139600
https://www.sciencedirect.com/science/a ... 972033120X
"At 144 h, several genes related to thyroid hormones that are essential for neurodevelopment, including corticotropin releasing hormone b (crhb), iodothyronine deiodinase 3a (dio3a), thyroid-stimulating hormone receptor (tshr) and nkx2 homeobox1 (nkx 2.1), were up-regulated by 8:8 PFPiA at 5.79 μM."
Kim J, Lee G, Lee YM, Zoh KD, Choi K - "Thyroid disrupting effects of perfluoroundecanoic acid and perfluorotridecanoic acid in zebrafish (Danio rerio) and rat pituitary (GH3) cell line" Chemosphere 262:128012 (2021) doi: 10.1016/j.chemosphere.2020.128012
https://www.sciencedirect.com/science/a ... 3520322074
"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)."
Liu M, Yi S, Chen P, Chen M, Zhong W, Yang J, Sun B, Zhu L - "Thyroid endocrine disruption effects of perfluoroalkyl phosphinic acids on zebrafish at early development" Sci Total Environ 676:290-297 (2019) doi: 10.1016/j.scitotenv.2019.04.177
https://www.sciencedirect.com/science/a ... 9719317061
"Perfluoroalkyl phosphinic acids (PFPiAs, including 6:6, 6:8 and 8:8 PFPiAs) are one kind of emerging perfluoroalkyl substances and usually used as leveling and wetting agents in household cleaning products and pesticide formulations...8:8 PFPiA significantly promoted the gene expressions corresponding to THs transport, metabolism and action (transthyretin, ttr; uridine diphosphate glucuronosyltransferase, ugt1ab; deiodinases, dio1 and dio2; thyroid hormone receptors, trα and trβ)."
Martin MT, Brennan RJ, Hu W, Ayanoglu E, Lau C, Ren H, Wood CR, Corton JC, Kavlock RJ, Dix DJ - "Toxicogenomic study of triazole fungicides and perfluoroalkyl acids in rat livers predicts toxicity and categorizes chemicals based on mechanisms of toxicity" Toxicol Sci 97(2):595-613 (2007) doi: 10.1093/toxsci/kfm065
"PFOS caused significant Dio1 repression and Dio3 induction on day 5 of exposure, concordant with significant total T3 decreases only on day 5 and less severe depression of total and free T4 than PFOA."
Sarzo B, Ballesteros V, Iñiguez C, Manzano-Salgado CB, Casas M, Llop S, Murcia M, Guxens M, Vrijheid M, Marina LS, Schettgen T, Espada M, Irizar A, Fernandez-Jimenez N, Ballester F, Lopez-Espinosa MJ - "Maternal Perfluoroalkyl Substances, Thyroid Hormones, and DIO Genes: A Spanish Cross-sectional Study" Environ Sci Technol 55(16):11144–11154 (2021) doi: 10.1021/acs.est.1c01452
https://pubs.acs.org/doi/10.1021/acs.est.1c01452
Shi X, Liu C, Wu G, Zhou B - "Waterborne exposure to PFOS causes disruption of the hypothalamus-pituitary-thyroid axis in zebrafish larvae" Chemosphere 77(7):1010-8 (2009) doi: 10.1016/j.chemosphere.2009.07.074
https://www.sciencedirect.com/science/a ... 3509009126
"A significant increase in NIS and Dio1 gene expression was observed at 200 microg L(-1) PFOS exposure, while TG gene expression was down-regulated at 200 and 400 microg L(-1) PFOS exposure."
Sjöberg S - "Developmental effects of perfluoroalkyl acids (PFAS) in chicken" Master's Thesis (2017)
http://www.diva-portal.org/smash/get/di ... TEXT01.pdf
Song P, Li D, Wang X, Zhong X - "Effects of perfluorooctanoic acid exposure during pregnancy on the reproduction and development of male offspring mice" Andrologia 50(8):e13059 (2018) doi: 10.1111/and.13059
https://onlinelibrary.wiley.com/doi/10.1111/and.13059
"The expression of Dlk1-Dio3 imprinted gene cluster showed a decreasing trend, where Glt2, Rian and Dio3 gene expressions were significantly reduced (p < 0.05) on PND 21. Therefore, PFOA exposure during pregnancy reduces the number of survival offspring mice, damages testis, disrupts reproductive hormones and reduces the mRNA expressions of the Dlk1-Dio3 imprinted cluster in testis."
Vongphachan V, Cassone CG, Wu D, Chiu S, Crump D, Kennedy SW - " Effects of perfluoroalkyl compounds on mRNA expression levels of thyroid hormone-responsive genes in primary cultures of avian neuronal cells" Toxicol Sci 120(2):392-402 (2011) doi: 10.1093/toxsci/kfq395
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061477/
"Several PFCs altered the mRNA expression levels of genes associated with the TH pathway in avian neuronal cells. Short-chained PFCs (less than eight carbons) altered the expression of TH-responsive genes (D2, D3, TTR, and RC3) in chicken embryonic neuronal cells to a greater extent than long-chained PFCs (more than or equal to eight carbons)."
Wang J, Shi G, Yao J, Sheng N, Cui R, Su Z, Guo Y, Dai J - "Perfluoropolyether carboxylic acids (novel alternatives to PFOA) impair zebrafish posterior swim bladder development via thyroid hormone disruption" Environ Int 134:105317 (2020) doi: 10.1016/j.envint.2019.105317
https://pubmed.ncbi.nlm.nih.gov/31733528/
"For genes related to TH synthesis, the transcription levels of dio2 increased in the PFOA, PFO3OA, and PFO5DoDA-treated groups."
Yi S, Wang J, Wang R, Liu M, Zhong W, Zhu L, Jiang G - "Structure-Related Thyroid Disrupting Effect of Perfluorooctanesulfonate-like Substances in Zebrafish Larvae" Environ Sci Technol (2024) 58(1):182-193. doi: 10.1021/acs.est.3c07003 3.
https://pubs.acs.org/doi/10.1021/acs.est.3c07003
"PFOS-like substances could competitively replace THs to bind with TH plasma and membrane transporters, thereby disrupting TH transport and action, respectively. Moreover, they are also potent to disrupt TH synthesis and activation through Na+/K+-dependent transport of I- or competitive binding to the sites of deiodinases."
Yu WG, Liu W, Jin YH - "Effects of perfluorooctane sulfonate on rat thyroid hormone biosynthesis and metabolism" Environ Toxicol Chem 28(5):990-6 (2009) doi: 10.1897/08-345.1
https://setac.onlinelibrary.wiley.com/d ... 7/08-345.1
"Serum total T4 level decreased significantly at all applied dosages, whereas total T3 level increased markedly only at 1.7 mg/L of PFOS. No statistically significant toxic effects of PFOS on serum TSH were observed...Treatment with PFOS lowered hepatic DIO1 mRNA at 15.0 mg/L but increased thyroidal DIO1 mRNA dose dependently. The activity of TPO, NIS, and TSHR mRNA in thyroid were unaffected by PFOS treatment. These results indicate that increased hepatic T4 glucuronidation via UGT1A1 and increased thyroidal conversion of T4 to T3 via DIO1 were responsible in part for PFOS-induced hypothyroxinemia in rats."
Zhang S, Guo X, Lu S, He J, Wu Q, Liu X, Han Z, Xie P - "Perfluorohexanoic acid caused disruption of the hypothalamus-pituitary-thyroid axis in zebrafish larvae" Ecotoxicol Environ Saf 232:113283 (2022) doi: 10.1016/j.ecoenv.2022.113283
https://www.sciencedirect.com/science/a ... 1322001233
"Treatment with PFHxA significantly downregulated dio2 gene transcription (0.79- and 0.79-fold) in the 2.4 and 12 mg/L exposure groups. The level of the dio1 gene was also decreased when exposed to 12 mg/L PFHxA."
Zhang S, Guo X, Lu S, Sang N, Li G, Xie P, Liu C, Zhang L, Xing Y - "Exposure to PFDoA causes disruption of the hypothalamus-pituitary-thyroid axis in zebrafish larvae" Environ Pollut 235:974-982 (2018) doi: 10.1016/j.envpol.2018.01.015
https://www.sciencedirect.com/science/a ... 9117326453
BI-PHASIC: "Iodothyronine deiodinases (dio2) was upregulated in the 1.2 mg/L PFDoA group...Upregulation and downregulation of iodothyronine deiodinases (dio1) gene expression were observed upon the treatment of 1.2 mg/L and 6 mg/L PFDoA, respectively."
see also: rT3 (D3)
Chang SC, Thibodeaux JR, Eastvold ML, Ehresman DJ, Bjork JA, Froehlich JW, Lau C, Singh RJ, Wallace KB, Butenhoff JL - "Thyroid hormone status and pituitary function in adult rats given oral doses of perfluorooctanesulfonate (PFOS)" Toxicology 243(3):330-9 (2008) doi: 10.1016/j.tox.2007.10.014
https://www.sciencedirect.com/science/a ... 83X0700742
Flynn RW, Hoover G, Iacchetta M, Guffey S, de Perre C, Huerta B, Li W, Hoverman JT, Lee L, Sepúlveda MS - "Comparative Toxicity of Aquatic Per- and Polyfluoroalkyl Substance Exposure in Three Species of Amphibians" Environ Toxicol Chem 41(6):1407-1415 (2022) doi: 10.1002/etc.5319
https://setac.onlinelibrary.wiley.com/d ... 2/etc.5319
SEE also:
Fluoride - D1, D2, and D3 deiodinases
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