Dibutyl phthalate-induced neurotoxicity in the brain of immature and mature rat offspring

Brain Dev. 2014 Sep;36(8):653-60. doi: 10.1016/j.braindev.2013.09.002. Epub 2013 Sep 26.

Abstract

Purpose: We aim to investigate the neurotoxicity induced by perinatal exposure of dibutyl phthalate (DBP) on the immature and mature offspring animals using a rodent model.

Methods: Pregnant rats were given intragastric administration of 500mg/kg body weight DBP daily from gestational day 6 to postnatal day 21 while control animals received the same volume of edible corn oil. Serum estradiol and testosterone levels of the offspring were evaluated. Protein levels of AROM, ER-β, BDNF and p-CREB in the hippocampus were also measured.

Results: Perinatal exposure of DBP significantly up-regulated the serum estradiol levels in both immature and mature offspring rats. DBP exposure also significantly down-regulated the testosterone levels in immature male and female rats and mature male rats but had no influence on the testosterone levels in mature female rats. DBP exposure up-regulated AROM, but down-regulated ER-β, BDNF and p-CREB expression in the hippocampus of immature rat offspring, while it had no influence on the levels of these proteins in the mature animals.

Conclusions: Perinatal exposure of DBP could induce neurotoxicity in immature offspring rats through regulation of AROM, ER-β, BDNF and p-CREB expression, while it has no influence on mature offspring animals.

Keywords: DBP; Hippocampus; Neurotoxicity; Perinatal exposure; Sex hormone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Aromatase / metabolism
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Dibutyl Phthalate / toxicity*
  • Estradiol / blood
  • Estrogen Receptor beta / metabolism
  • Female
  • Hippocampus / drug effects*
  • Hippocampus / embryology
  • Hippocampus / growth & development
  • Hippocampus / metabolism
  • Male
  • Plasticizers / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Testosterone / blood

Substances

  • Brain-Derived Neurotrophic Factor
  • Cyclic AMP Response Element-Binding Protein
  • Estrogen Receptor beta
  • Plasticizers
  • Dibutyl Phthalate
  • Testosterone
  • Estradiol
  • Aromatase