The flame retardant DE-71 (a mixture of polybrominated diphenyl ethers) inhibits human differentiated thyroid cell function in vitro

PLoS One. 2017 Jun 23;12(6):e0179858. doi: 10.1371/journal.pone.0179858. eCollection 2017.

Abstract

Background: Normal thyroid function is essential for general growth and metabolism, but can be affected by endocrine disrupting chemicals (EDCs). Polybrominated diphenyl ethers (PBDEs) have been used worldwide to reduce flammability in different materials and are suspected to be EDCs. The production of the commercial Penta- and OctaBDE mixtures is banned, but DecaBDEs and existing products may leak PBDEs into the environment. Our aim was to investigate the effect of the PentaBDE mixture DE-71 on human thyroid cells in vitro.

Materials and methods: Primary human thyroid cells were obtained as paraadenomatous tissue and cultured in monolayers. The influence of DE-71 on cyclic adenosine monophosphate (cAMP) and thyroglobulin (Tg) production was examined in the culture medium by competitive radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Real-time quantitative PCR analysis of thyroid-specific genes was performed on the exposed cell cultures. PBDE concentrations were determined in cellular and supernatant fractions of the cultures.

Results: DE-71 inhibited Tg-release from TSH-stimulated thyrocytes. At 50 mg/L DE-71, mean Tg production was reduced by 71.9% (range: 8.5-98.7%), and cAMP by 95.1% (range: 91.5-98.8%) compared to controls). Expression of mRNA encoding Tg, TPO and TSHr were significantly inhibited (p<0.0001, p = 0.0079, and p = 0.0002, respectively). The majority of DE-71 added was found in the cell fraction. No cytotoxicity was found.

Conclusions: DE-71 inhibited differentiated thyroid cell functions in a two phase response manner and a concentration-dependent inhibition of Tg and cAMP production, respectively, as well as expression of mRNA encoding Tg, TPO and TSHr. Our findings suggest an inhibiting effect of PBDEs on thyroid cells.

MeSH terms

  • Adenoma / surgery
  • Cells, Cultured
  • Cyclic AMP / metabolism
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Endocrine Disruptors / pharmacology*
  • Enzyme-Linked Immunosorbent Assay
  • Flame Retardants / pharmacology*
  • Halogenated Diphenyl Ethers / pharmacology*
  • Humans
  • RNA, Messenger / metabolism
  • Radioimmunoassay
  • Real-Time Polymerase Chain Reaction
  • Thyroglobulin / metabolism
  • Thyroid Gland / drug effects*
  • Thyroid Gland / metabolism
  • Thyroid Neoplasms / surgery
  • Thyroidectomy

Substances

  • Endocrine Disruptors
  • Flame Retardants
  • Halogenated Diphenyl Ethers
  • RNA, Messenger
  • pentabromodiphenyl ether
  • Thyroglobulin
  • Cyclic AMP

Grants and funding

Ulla Feldt-Rasmussen received funding as main supervisor on the scholarship project “Interaction between thyroid autoimmunity and endocrine disrupting chemicals” by the Novo Nordisk foundation (application number: 13495), for Thit Mynster Kronborg’s salary. Ulla Feldt-Rasmussen further received funding for research salary, equipment and material from the local region’s (RegionH, R129-A4222) research fund, from Arvid Nilsson’s Fund, Novo Nordisk Foundation (application number 8005 and 14266) and Danish Council for Independent Research (0602-01959B). Thit Mynster Kronborg received funding from the Danish Foundation ”Musikforlæggernes Agnes og Knut Mørks fond” (35108-001), which sponsored equipment and materials. None of the funding agencies had any role or influence on this study, and none of the authors had any conflicts of interest.