Developmental origins of adult disease

Pediatr Clin North Am. 2009 Jun;56(3):449-66, Table of Contents. doi: 10.1016/j.pcl.2009.03.004.


Intrauterine growth retardation (IUGR) has been linked to development of type 2 diabetes in adulthood. Using a rat model, we tested the hypothesis that uteroplacental insufficiency disrupts the function of the electron transport chain in the fetal beta-cell and leads to a debilitating cascade of events. The net result is progressive loss of beta-cell function and eventual development of type 2 diabetes in the adult. Studies in the IUGR rat demonstrate that an abnormal intrauterine environment induces epigenetic modifications of key genes regulating beta-cell development; experiments directly link chromatin remodeling with suppression of transcription. Future research will be directed at elucidating the mechanisms underlying epigenetic modifications in offspring.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adult
  • Animals
  • B-Lymphocytes / physiology*
  • Birth Weight / physiology
  • Chromatin Assembly and Disassembly
  • Diabetes Mellitus, Type 2 / genetics*
  • Disease Models, Animal
  • Epigenesis, Genetic*
  • Female
  • Fetal Growth Retardation / genetics*
  • Fetal Growth Retardation / immunology
  • Gene Expression
  • Humans
  • Insulin-Secreting Cells / pathology*
  • Male
  • Mitochondria / physiology
  • Oxidative Stress
  • Rats