Interaction of PFOS and BDE-47 co-exposure on thyroid hormone levels and TH-related gene and protein expression in developing rat brains

Toxicol Sci. 2011 Jun;121(2):279-91. doi: 10.1093/toxsci/kfr068. Epub 2011 Mar 23.

Abstract

Perfluorooctane sulfonate (PFOS) and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) are two persistent environmental contaminants that are toxic to developing nervous systems, particularly via their disruption of thyroid hormone (TH) function. To investigate whether an interaction existed between PFOS and BDE-47 on TH-mediated pathways, adult female Wistar rats were exposed to 3.2 and 32 mg/kg of PFOS or BDE-47 in their diet and co-exposed to a combination of each chemical (3.2 mg/kg) from gestational day 1 to postnatal day (PND) 14. Serum and brain tissues from both male and female neonates were collected on PNDs 1, 7, and 14 to examine TH-regulated gene and protein expression. The results revealed that (1) a significant accumulation difference occurred between the two chemicals; (2) On a equimolar basis, BDE-47 and PFOS affected serum total triiodothyronine and total thyroxine differently in adults and offspring; (3) there were region-specific and exposure- and time-dependent alterations in TH concentrations and tested gene and protein expression levels; and (4) interaction for the combined chemicals was only observed for brain-derived neurotrophic factor (BDNF), which exhibited a synergistic effect on PND 1 in the cortex and an antagonistic effect on PND 14 in the hippocampus. Our results suggest a complex TH-mediated gene and protein response to BDE-47 and/or PFOS exposure that seems little related to TH homeostasis and that little combined interaction of co-exposures was observed except on BDNF. The underlying mechanisms remain uncertain but seem to involve more actions than just TH-regulated pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkanesulfonic Acids / chemistry
  • Alkanesulfonic Acids / toxicity*
  • Animals
  • Animals, Newborn
  • Brain-Derived Neurotrophic Factor / metabolism
  • Drug Interactions
  • Female
  • Fluorocarbons / chemistry
  • Fluorocarbons / toxicity*
  • GAP-43 Protein / genetics
  • GAP-43 Protein / metabolism
  • Gene Expression Regulation, Developmental
  • Halogenated Diphenyl Ethers
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Male
  • Neural Cell Adhesion Molecules / genetics
  • Neural Cell Adhesion Molecules / metabolism
  • Polybrominated Biphenyls / chemistry
  • Polybrominated Biphenyls / toxicity*
  • Polymerase Chain Reaction
  • Pregnancy
  • Prenatal Exposure Delayed Effects / blood
  • Prenatal Exposure Delayed Effects / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Thyroid Gland / drug effects
  • Thyroid Gland / pathology
  • Thyroid Hormones / blood*
  • Thyroid Hormones / genetics*
  • Thyroxine / blood
  • Triiodothyronine / blood

Substances

  • Alkanesulfonic Acids
  • Brain-Derived Neurotrophic Factor
  • Fluorocarbons
  • GAP-43 Protein
  • Halogenated Diphenyl Ethers
  • Kruppel-Like Transcription Factors
  • Neural Cell Adhesion Molecules
  • Polybrominated Biphenyls
  • RNA, Messenger
  • Thyroid Hormones
  • Triiodothyronine
  • 2,2',4,4'-tetrabromodiphenyl ether
  • Klf9 protein, rat
  • perfluorooctane sulfonic acid
  • Thyroxine