Prenatal Maternal Stress Predicts Methylation of Genes Regulating the Hypothalamic-Pituitary-Adrenocortical System in Mothers and Newborns in the Democratic Republic of Congo

Darlene A Kertes, Hayley S Kamin, David A Hughes, Nicole C Rodney, Samarth Bhatt, Connie J Mulligan

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Exposure to stress early in life permanently shapes activity of the hypothalamic-pituitary-adrenocortical (HPA) axis and the brain. Prenatally, glucocorticoids pass through the placenta to the fetus with postnatal impacts on brain development, birth weight (BW), and HPA axis functioning. Little is known about the biological mechanisms by which prenatal stress affects postnatal functioning. This study addresses this gap by examining the effect of chronic stress and traumatic war-related stress on epigenetic changes in four key genes regulating the HPA axis in neonatal cord blood, placenta, and maternal blood: CRH, CRHBP, NR3C1, and FKBP5. Participants were 24 mother-newborn dyads in the conflict-ridden region of the eastern Democratic Republic of Congo. BW data were collected at delivery and maternal interviews were conducted to assess culturally relevant chronic and war-related stressors. Chronic stress and war trauma had widespread effects on HPA axis gene methylation, with significant effects observed at transcription factor binding (TFB) sites in all target genes tested. Some changes in methylation were unique to chronic or war stress, whereas others were observed across both stressor types. Moreover, stress exposures impacted maternal and fetal tissues differently, supporting theoretical models that stress impacts vary according to life phase. Methylation in several NR3C1 and CRH CpG sites, all located at TFB sites, was associated with BW. These findings suggest that prenatal stress exposure impacts development via epigenetic changes in HPA axis genes.

Original languageEnglish
Pages (from-to)61-72
Number of pages12
JournalChild Development
Volume87
Issue number1
DOIs
Publication statusPublished - 28 Jan 2016

Keywords

  • Adult
  • Carrier Proteins/metabolism
  • Corticotropin-Releasing Hormone/metabolism
  • DNA Methylation/genetics
  • Democratic Republic of the Congo
  • Epigenesis, Genetic/genetics
  • Female
  • Humans
  • Hypothalamo-Hypophyseal System/metabolism
  • Infant, Newborn
  • Male
  • Pituitary-Adrenal System/metabolism
  • Pregnancy
  • Pregnancy Complications/metabolism
  • Psychological Trauma/metabolism
  • Receptors, Glucocorticoid/metabolism
  • Stress, Psychological/metabolism
  • Tacrolimus Binding Proteins/metabolism
  • Young Adult

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