PFOS-induced thyroid hormone system disrupted rats display organ-specific changes in their transcriptomes. (15th July 2022)

• Record Type: Journal Article
• Authors: Davidsen, Nichlas; Ramhøj, Louise; Lykkebo, Claus Asger; Kugathas, Indusha; Poulsen, Rikke; Rosenmai, Anna Kjerstine; Evrard, Bertrand; Darde, Thomas A.; Axelstad, Marta; Bahl, Martin Iain; Hansen, Martin; Chalmel, Frederic; Licht, Tine Rask; Svingen, Terje
• Is Part Of: Environmental pollution. Volume 305(2022)
• Publication Date: 2022-07-15
• Subjects: PFOS -- Thyroid hormone -- Transcriptomics -- Vancomycin -- Endocrine disrupting chemicals -- Perfluorooctane sulfonate -- PFAS -- Perfluoroalkyl -- Thyroid -- HPT-axis; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2022.119340
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Perfluorooctanesulfonic acid (PFOS) is a persistent anthropogenic chemical that can affect the thyroid hormone system in humans and animals. In adults, thyroid hormones (THs) are regulated by the hypothalamic-pituitary-thyroid (HPT) axis, but also by organs such as the liver and potentially the gut microbiota. PFOS and other xenobiotics can therefore disrupt the TH system at various locations and through different mechanisms. To start addressing this, we exposed adult male rats to 3 mg PFOS/kg/day for 7 days and analysed effects on multiple organs and pathways simultaneously by transcriptomics. This included four primary organs involved in TH regulation, namely hypothalamus, pituitary, thyroid, and liver. To investigate a potential role of the gut microbiota in thyroid hormone regulation, two additional groups of animals were dosed with the antibiotic vancomycin (8 mg/kg/day), either with or without PFOS. PFOS exposure decreased thyroxine (T4) and triiodothyronine (T3) without affecting thyroid stimulating hormone (TSH), resembling a state of hypothyroxinemia. PFOS exposure resulted in 50 differentially expressed genes (DEGs) in the hypothalamus, 68 DEGs in the pituitary, 71 DEGs in the thyroid, and 181 DEGs in the liver. A concomitant compromised gut microbiota did not significantly change effects of PFOS exposure. Organ-specific DEGs did not align with TH regulating genes; however, genes associated with vesicle transport and neuronal signaling were affected in the hypothalamus, and phase I and phase II metabolism in the liver. This suggests that a decrease in systemic TH levels may activate the expression of factors altering trafficking, metabolism and excretion of TH. At the transcriptional level, little evidence suggests that the pituitary or thyroid gland is involved in PFOS-induced TH system disruption. Graphical abstract: Image 1 Highlights: PFOS exposure decrease T4, T3, rT3 and T1Ac in adult male rats. PFOS reduces thyroid hormone concentrations without activating the HPT-axis. PFOS alters gene expression in hypothalamus, pituitary, thyroid and liver. PFOS dysregulates axon function and vesicle transport genes in hypothalamus. Compromised gut microbiome had no significant effect on PFOS-induced DEGs.