Placental epigenetic patterning of glucocorticoid response genes is associated with infant neurodevelopment

Epigenomics. 2015 Aug;7(5):767-79. doi: 10.2217/epi.15.28. Epub 2015 Sep 7.

Abstract

Aim: To determine associations between methylation of NR3C1, HSD11B2, FKBP5 and ADCYAP1R1 and newborn neurobehavioral outcomes.

Methods: In 537 newborns, placental methylation was quantified using bisulfite pyrosequencing. Profiles of neurobehavior were derived via the Neonatal Intensive Care Unit Network Neurobehavioral Scales. Using exploratory factor analysis, the relationships between methylation factor scores and neurobehavioral profiles were examined.

Results: Increased scores of the factor characterized by NR3C1 methylation were associated with membership in a reactive, poorly regulated profile (odds ratio: 1.47; 95% CI: 1.00-2.18), while increased scores of the factor characterized by HSD11B2 methylation reduced this risk.

Conclusion: These results suggest that coordinated regulation of these genes influences neurobehavior and demonstrates the importance of examining these alterations in a harmonized fashion.

Keywords: ADCYAP1R1; FKBP5; HSD11B2; NR3C1; fetal basis of adult disease; glucocorticoids; neurobehavior; placenta.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 2 / genetics
  • Adolescent
  • Adult
  • CpG Islands / genetics
  • DNA Methylation
  • Epigenesis, Genetic / drug effects
  • Epigenesis, Genetic / genetics*
  • Epigenomics / methods*
  • Female
  • Gestational Age
  • Glucocorticoids / metabolism*
  • Glucocorticoids / pharmacology
  • Humans
  • Infant Behavior / drug effects
  • Infant Behavior / physiology
  • Infant, Newborn
  • Male
  • Maternal Age
  • Nervous System / drug effects
  • Nervous System / growth & development
  • Nervous System / metabolism*
  • Placenta / metabolism*
  • Pregnancy
  • Receptors, Glucocorticoid / genetics
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / genetics
  • Regression Analysis
  • Tacrolimus Binding Proteins / genetics
  • Young Adult

Substances

  • ADCYAP1R1 protein, human
  • Glucocorticoids
  • NR3C1 protein, human
  • Receptors, Glucocorticoid
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2
  • HSD11B2 protein, human
  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 5