Effects of maternal exposure to BDE209 on neuronal development and transcription of iodothyronine deiodinase in offspring mice

Toxicol Mech Methods. 2019 Oct;29(8):569-579. doi: 10.1080/15376516.2019.1624906. Epub 2019 Jun 19.

Abstract

The present study investigated the alterations in nerve function and its potential mechanism of offspring result from the decabromodiphenyl ether (BDE209) orally gavage (0, 1.5, and 225 mg/kg.d body weight) in pregnant and lactating mice. Weight gain and litter size of maternal mice and body weight of offspring were examined. Learning and memory abilities of offspring were tested by the Morris water maze experiment. Thyroid hormones (THs) concentrations in peripheral blood of offspring were detected by the chemiluminescence enzyme immunoassay. Relative mRNA expression of type 1 iodothyronine deiodinase (dio1), type 2 iodothyronine deiodinase (dio2), and type 3 iodothyronine deiodinase (dio3) in the livers and brains of offspring were measured by QRT-PCR (quantitative real-time polymerase chain reaction). Protein expression of dio3 in the livers and brains of offspring was measured by Western blot. All indexes of offspring were tested at postnatal day (PND) 21 and PND 60, respectively. As a result, administration of BDE209 decreased weight gain and litter size of maternal mice, and reduced body weight of offspring mice, prolonged escape latency and declined guardant time of offspring in the Morris water maze experiment. Moreover, BDE209 elevated serum levels of total thyroxine (T4), total triiodothyronine (T3), free T4, and free T3 in offspring. In addition, maternal exposure to BDE209 inhibited dio1, dio2, dio3 mRNA expression in the livers of offspring, while elevated dio1 mRNA expression and reduced dio3 mRNA expression in the brains of offspring. BDE209 also inhibited the protein expression of dio3 in the livers and brains of offspring. These results indicate that BDE209 exposure to pregnant and lactating mice can cause disruption in serum THs of offspring by altering mRNA and protein expression of iodothyronine deiodinases, which might consequently result in neurologic impairment of offspring mice.

Keywords: BDE209; developmental neurotoxicity; iodothyronine deiodinase; learning; memory abilities; thyroid hormones.

MeSH terms

  • Animals
  • Animals, Newborn
  • Environmental Pollutants / toxicity*
  • Female
  • Halogenated Diphenyl Ethers / toxicity*
  • Iodide Peroxidase / genetics*
  • Lactation
  • Male
  • Maternal Exposure / adverse effects*
  • Maze Learning / drug effects
  • Mice, Inbred ICR
  • Neurons / drug effects*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Swimming
  • Thyroid Hormones / blood
  • Transcription, Genetic / drug effects*

Substances

  • Environmental Pollutants
  • Halogenated Diphenyl Ethers
  • Thyroid Hormones
  • Iodide Peroxidase
  • decabromobiphenyl ether