Uteroplacental insufficiency alters rat hippocampal cellular phenotype in conjunction with ErbB receptor expression

Pediatr Res. 2012 Jul;72(1):2-9. doi: 10.1038/pr.2012.32. Epub 2012 Feb 24.


Introduction: Uteroplacental insufficiency (UPI) produces significant neurodevelopmental deficits affecting the hippocampus of intrauterine growth-restricted (IUGR) offspring. IUGR males have worse deficits as compared with IUGR females. The exact mechanisms underlying these deficits are unclear. Alterations in hippocampal cellular composition along with altered expression of neural stem cell (NSC) differentiation molecules may underlie these deficits. We hypothesized that IUGR hippocampi would be endowed with altered neuronal, astrocytic, and immature oligodendrocytic proportions at birth, with males showing greater cellular deficits. We further hypothesized that UPI would perturb rat hippocampal expression of ErbB receptors (ErbB-Rs) and neuregulin 1 (NRG1) at birth and at weaning to account for the short- and long-term IUGR neurological sequelae.

Methods: A well-established rat model of bilateral uterine artery ligation at embryonic day 19.5 was used to induce IUGR.

Results: As compared with gender-matched controls, IUGR offspring have altered hippocampal neuronal, astrocytic, and immature oligodendrocytic composition in a subregion- and gender-specific manner at birth. In addition, IUGR hippocampi have altered receptor type- and gender-specific ErbB-R expression at birth and at weaning.

Discussion: These cellular and molecular alterations may account for the neurodevelopmental complications of IUGR and for the male susceptibility to worse neurologic outcomes.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Cell Differentiation / physiology
  • Female
  • Fetal Growth Retardation / etiology
  • Fetal Growth Retardation / physiopathology*
  • Hippocampus / cytology
  • Hippocampus / physiopathology*
  • Ligation
  • Male
  • Microscopy, Fluorescence
  • Neural Stem Cells / metabolism
  • Neuregulin-1 / metabolism
  • Oligodendroglia / metabolism
  • Placental Insufficiency / physiopathology*
  • Pregnancy
  • Rats
  • Receptor, ErbB-2 / metabolism*
  • Sex Factors
  • Uterine Artery / surgery


  • Neuregulin-1
  • Erbb2 protein, rat
  • Receptor, ErbB-2