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

INTRODUCTION: Uteroplacental insufficiency (UPI) produces significant neurodevelopmental deficits affecting the hippocampus of intrauterine growth restricted (IUGR) offspring. IUGR males have worse deficits compared to 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. HYPOTHESIS: 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 (E) 19.5 was used to induce IUGR. RESULTS: Compared to 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. CONCLUSIONS: These cellular and molecular alterations may account for the neurodevelopmental complications of IUGR and for the male susceptibility to worse neurologic outcomes.