Intrauterine exposure to maternal stress alters Bdnf IV DNA methylation and telomere length in the brain of adult rat offspring

Int J Dev Neurosci. 2017 Nov;62:56-62. doi: 10.1016/j.ijdevneu.2017.03.007. Epub 2017 Mar 19.


DNA methylation (addition of methyl groups to cytosines) and changes in telomere length (TTAGGG repeats on the ends of chromosomes) are two molecular modifications that result from stress and could contribute to the long-term effects of intrauterine exposure to maternal stress on offspring behavior. Here, we measured methylation of DNA associated with the Brain-derived neurotrophic factor (Bdnf) gene, a gene important in development and plasticity, and telomere length in the brains of adult rat male and female offspring whose mothers were exposed to unpredictable and variable stressors throughout gestation. Males exposed to prenatal stress had greater methylation (Bdnf IV) in the medial prefrontal cortex (mPFC) compared to non-stressed male controls and stressed females. Further, prenatally-stressed animals had shorter telomeres than controls in the mPFC. Together findings indicate a long-term impact of prenatal stress on brain DNA methylation and telomere biology with relevance for behavioral and health outcomes, and contribute to a growing literature linking stress to intergenerational molecular changes.

Keywords: DNA methylation; Maternal stress; Prenatal stress; Telomere length.

MeSH terms

  • Analysis of Variance
  • Animals
  • Brain / metabolism*
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • DNA Methylation / genetics*
  • Epigenesis, Genetic / physiology*
  • Female
  • Male
  • Pregnancy
  • Pregnancy Outcome
  • Prenatal Exposure Delayed Effects / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Sex Factors
  • Stress, Psychological* / genetics
  • Stress, Psychological* / metabolism
  • Stress, Psychological* / pathology
  • Telomere Homeostasis / physiology*


  • Brain-Derived Neurotrophic Factor
  • BDNF protein, human