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全氟辛烷磺酸(PFOS)会破坏发育中的大鼠甲状腺中的钙黏蛋白-16。

Perfluorooctanesulfonic acid (PFOS) disrupts cadherin-16 in the developing rat thyroid gland.

作者信息

Davidsen Nichlas, Ramhøj Louise, Ballegaard Anne-Sofie Ravn, Rosenmai Anna Kjerstine, Henriksen Cecillie Sofie, Svingen Terje

机构信息

National Food Institute, Technical University of Denmark, Kgs. Lyngby DK-2800, Denmark.

出版信息

Curr Res Toxicol. 2024 Feb 6;6:100154. doi: 10.1016/j.crtox.2024.100154. eCollection 2024.

Abstract

Perfluorooctanesulfonic acid (PFOS) can disrupt the thyroid hormone (TH) system in rodents, potentially affecting perinatal growth and neurodevelopment. Some studies also suggest that gestational exposure to PFOS can lead to lower TH levels throughout life, indicating that PFOS may compromise thyroid gland development. To address this question, we utilized a rat thyroid gland culture system to study direct effects of PFOS on the developing thyroid. No significant changes to follicular structure or size were observed with 1 µM or 10 µM PFOS exposure. However, the transcription factor , together with and , were upregulated whereas the key transcription factor and its downstream target gene were significantly downregulated at the transcript level, observed with both RT-qPCR and RNAscope. Notably, expression was not uniformly downregulated across -postive cells, but instead displayed a patchy expression pattern across the thyroid gland. This is a significant change in expression pattern compared to control thyroids where is expressed relatively uniformly The disrupted expression pattern was also seen at the protein level. This suggests that PFOS exposure can impact follicular growth and structure. Compromised follicle integrity, if irreversible, could help explain reduced TH synthesis postnatally. This view is supported by observed changes to and expression, two factors that play a role in TH synthesis.

摘要

全氟辛烷磺酸(PFOS)可扰乱啮齿动物的甲状腺激素(TH)系统,可能影响围产期生长和神经发育。一些研究还表明,孕期接触PFOS可导致终生TH水平降低,这表明PFOS可能损害甲状腺发育。为解决这个问题,我们利用大鼠甲状腺培养系统研究PFOS对发育中甲状腺的直接影响。暴露于1µM或10µM PFOS时,未观察到滤泡结构或大小有显著变化。然而,转录因子以及和被上调,而关键转录因子及其下游靶基因在转录水平上显著下调,这在RT-qPCR和RNAscope中均有观察到。值得注意的是,表达在阳性细胞中并非均匀下调,而是在整个甲状腺中呈现出斑驳的表达模式。与对照甲状腺相比,这是一种显著的表达模式变化,对照甲状腺中表达相对均匀。在蛋白质水平上也观察到了这种破坏的表达模式。这表明PFOS暴露可影响滤泡生长和结构。如果滤泡完整性受损且不可逆转,则有助于解释出生后TH合成减少。观察到的和表达的变化支持了这一观点,这两个因素在TH合成中起作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e21d/10861841/1bbc2fd02bc3/ga1.jpg

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