Distinct transcriptional profiles in rat thyroid glands after developmental exposure to three in vitro thyroperoxidase inhibiting chemicals

Anna Kjerstine Rosenmai*, Terje Svingen, Bertrand Evrard, Khanh Hoang Nguyen, Camilla Nielsen, Marta Axelstad, Frédéric Chalmel, Louise Ramhøj

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

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..
Original languageEnglish
Article number110938
JournalGenomics
Volume116
Issue number5
Number of pages8
ISSN0888-7543
DOIs
Publication statusPublished - 2024

Keywords

  • Thyroperoxidase
  • Enzyme inhibition
  • Transcriptomics
  • Thyroid hormone system disruption
  • Toxicity profiling
  • Thyroxine
  • Thyroid stimulating hormone

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