title: Intrauterine Growth Restriction: Effects on Neural Precursor Cell Proliferation and Angiogenesis in the Foetal Subventricular Zone.
abstract: Exposure to adverse prenatal factors can result in abnormal brain development, contributing to the aetiology of several neurological disorders. Intrauterine insults could occur during neurogenesis and gliogenesis, disrupting these events. Here we investigate the effects of chronic placental insufficiency (CPI) on cell proliferation and the microenvironment in the subventricular zone (SVZ). At 30 days of gestation (DG; term ∼67 DG), CPI was induced in pregnant guinea pigs via unilateral uterine artery ligation to produce growth-restricted (GR) foetuses (n = 7); controls (n = 6) were from the unoperated horn. At 60 DG, foetal brains were stained immunohistochemically to identify proliferating cells (Ki67), immature neurons (polysialylated neuronal cell adhesion molecule), astrocytes (glial fibrillary acidic protein), microglia (ionised calcium-binding adaptor molecule-1, Iba-1) and the microvasculature (von Willebrand factor) in the SVZ. There was no overall difference (p > 0.05) in the total number of Ki67-immunoreactive (IR) cells, the percentage of SVZ occupied by blood vessels or the density of Iba-1-IR microglia in control versus GR foetuses. However, regression analysis across both groups revealed that both the number of Ki67-IR cells and the percentage of SVZ occupied by blood vessels in the ventral SVZ were negatively correlated (p < 0.05) with brain weight. Furthermore, in the SVZ (dorsal and ventral) the density of blood vessels positively correlated (p < 0.05) with the number of Ki67-IR cells. Double-labelling immunofluorescence suggested that the majority of proliferating cells were likely to be neural precursor cells. Thus, we have demonstrated an association between angiogenesis and neurogenesis in the foetal neurogenic niche and have identified a window of opportunity for the administration of trophic support to enhance a neuroregenerative response.
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Vic., Australia.
authors.forename: Mary
authors.initials: M
authors.lastname: Tolcos
authors.forename: Rachel
authors.initials: R
authors.lastname: Markwick
authors.forename: Rachael
authors.initials: R
authors.lastname: O'Dowd
authors.forename: Veronica
authors.initials: V
authors.lastname: Martin
authors.forename: Ann
authors.initials: A
authors.lastname: Turnley
authors.forename: Sandra
authors.initials: S
authors.lastname: Rees
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology*; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D006168:Guinea Pigs; D020547:Lateral Ventricles / Q000254:growth & development*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D010927:Placental Insufficiency / Q000503:physiopathology; D011247:Pregnancy