Thyroid hormone disruption and cognitive impairment in rats exposed to PBDE during postnatal development

Reprod Toxicol. 2016 Aug:63:114-24. doi: 10.1016/j.reprotox.2016.05.017. Epub 2016 May 24.

Abstract

Polybrominated diphenyl ether flame-retardants (PBDEs) are thyroid-disrupting environmental chemicals. We investigated the effects of postnatal exposure to DE-71 (a mixture of tetra- and penta-brominated congeners), n-propylthiouracil (PTU) and thyroxine (T4) replacement on open-field (OF) and radial maze (RAM) tests. Wistar rats (5 males/5 females per litter, 32 litters) were treated orally (PND 5-22) with PTU (4mg/kg bw/d), DE-71 (30mg/kg bw/d), with and without co-administration of T4 (15μg/kg bw/d, sc). PTU depressed T4 serum levels and body weight gain and enlarged thyroid gland. Although decreasing T4 levels, DE-71 did not change thyroid and body weights. PTU-treated rats showed hyperactivity (PND 42 and 70), and working and reference memory learning deficits (RAM, PND 100). Although not altering motor activity and working memory, DE-71 caused a reference memory deficit (females only). T4 co-administration averted hypothyroxinemia and long-term cognitive deficits caused by PTU and DE-71.

Keywords: Behavior; DE-71; Developmental neurotoxicity; Flame retardants; Learning; Liver enzyme induction; PBDEs; Polybrominated diphenyl ether; Thyroid function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain / drug effects
  • Brain / growth & development
  • Cognitive Dysfunction / chemically induced
  • Cytochrome P-450 CYP1A1 / metabolism
  • Cytochrome P-450 CYP2B1 / metabolism
  • Environmental Pollutants / toxicity*
  • Female
  • Flame Retardants / toxicity*
  • Glucuronosyltransferase / genetics
  • Halogenated Diphenyl Ethers / toxicity*
  • Liver / drug effects
  • Liver / enzymology
  • Male
  • Rats, Wistar
  • Thyroxine / blood*

Substances

  • Environmental Pollutants
  • Flame Retardants
  • Halogenated Diphenyl Ethers
  • Ugt1a1 protein, rat
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP2B1
  • Glucuronosyltransferase
  • Thyroxine