Development and primary characterization of a human thyroid organoid in vitro model for thyroid metabolism investigation

Mol Cell Endocrinol. 2024 Dec 1:594:112377. doi: 10.1016/j.mce.2024.112377. Epub 2024 Sep 27.

Abstract

A 3D thyroid model was developed to address the limitations of 2D cultures and study the effects of compounds like 3-MNT on dehalogenase 1 (IYD) and metabolic activity. Morphology was assessed by TEM, and the expression of tissue-specific genes (TPO, TSHR, PAX8, TTF-1, NIS, IYD, TG) and metabolic features were analyzed using qRT-PCR, immunofluorescence, western blotting, ELISA, and LC-MS/MS, with and without TSH stimulus and 3-MNT treatment. Confocal and TEM analyses confirmed a follicle-like 3D structure. Expression of TPO, NIS, TG, TSH, and PAX markers was significantly higher (p < 0.05) in 3D versus 2D cultures, and ELISA showed increased TG protein production. 3-MNT treatment inhibited IYD activity, indicated by increased MIT and DIT in the media, and significantly altered (p < 0.05) NIS, TG, IYD, TSHR, and TPO expression. These findings suggest 3D thyroid cultures closely replicate tissue traits and functionality, providing a valuable tool for thyroid research.

Keywords: 3-MNT; Disruptors; IYD; Organoid; TSH; Thyroid.

MeSH terms

  • Humans
  • Iodide Peroxidase / genetics
  • Iodide Peroxidase / metabolism
  • Models, Biological
  • Organoids* / metabolism
  • Thyroid Gland* / cytology
  • Thyroid Gland* / metabolism
  • Thyrotropin / metabolism
  • Thyrotropin / pharmacology

Substances

  • Iodide Peroxidase
  • Thyrotropin