National Food Institute, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
National Food Institute, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
Genomics. 2024 Sep;116(5):110938. doi: 10.1016/j.ygeno.2024.110938. Epub 2024 Sep 16.
Thyroperoxidase (TPO) is central in thyroid hormone (TH) synthesis and inhibition can lead to TH deficiency. Many chemicals can inhibit TPO activity in vitro, but how this may manifest in the developing thyroid gland at the molecular level is unclear. Here, we characterized the thyroid gland transcriptome of male rats developmentally exposed to the in vitro TPO-inhibitors amitrole, 2-mercaptobenzimidazole (MBI), or cyanamide by use of Bulk-RNA-Barcoding (BRB) and sequencing. Amitrole exposure caused TH deficiency and 149 differentially expressed genes in the thyroid gland. The effects indicated an activated and growing thyroid gland. MBI caused intermittent changes to serum TH concentrations in a previous study and this was accompanied by 60 differentially expressed genes in the present study. More than half of these were also affected by amitrole, indicating that they could be early effect biomarkers of developmental TH system disruption due to TPO inhibition. Further work to validate the signature is needed, including assessment of substance independency and applicability domain.
甲状腺过氧化物酶（TPO）是甲状腺激素（TH）合成的核心，其抑制作用可导致 TH 缺乏。许多化学物质可以在体外抑制 TPO 的活性，但在分子水平上，这在发育中的甲状腺中是如何表现的尚不清楚。在这里，我们通过使用 Bulk-RNA-Barcoding（BRB）和测序，对雄性大鼠在发育过程中暴露于体外 TPO 抑制剂氨甲蝶呤、2-巯基苯并咪唑（MBI）或氰胺的甲状腺组织进行了转录组特征分析。氨甲蝶呤暴露导致 TH 缺乏和甲状腺中 149 个差异表达基因。这些影响表明甲状腺处于激活和生长状态。MBI 在先前的研究中导致血清 TH 浓度间歇性变化，本研究中也有 60 个差异表达基因。其中一半以上也受到氨甲蝶呤的影响，这表明它们可能是由于 TPO 抑制导致的发育中 TH 系统破坏的早期效应生物标志物。需要进一步验证该特征，包括评估物质独立性和适用域。
