Background Intrauterine growth restriction (IUGR) increases the risk of neurodevelopmental delay and causes neuroendocrine reprogramming in the affected newborn. Using a rat model of uteroplacental insufficiency (UPI) and IUGR, we have previously demonstrated that the hippocampus is vulnerable to IUGR-induced insult and in males has poorer outcome in learning and memory performance. It is not clear what changes in the hippocampus may be affected by IUGR.
Objective We therefore hypothesized that IUGR-induced stress affects neuronal development in the hippocampus.
Method Bilateral uterine artery ligation was performed on e19 pregnant Sprague-Dawley rats to induce IUGR through uteroplacental insufficiency (N = 4 litters). Pups were delivered by cesarean section at term. Brains were perfusion-fixed for immunofluorescence. Morphometric analysis was performed using an Automated/Metamorph Workstation, including counting of neurons per mm2 surface area and the density of GFAP, MBP, and synaptophysin/tissue area in the CA1, CA3, and dentate gyrus (DG). Neuronal density and average intensity of GFAP, MBP, or synaptophysin were quantified. The sections for counting were taken from the level of Bregma around −3.0, where all subzones of dorsal hippocampus were demarcated.
Results IUGR decreased neural density to 42 and 46% of control values in CA1 and CA3 hippocampal regions, respectively, in males. Parallel to neuronal loss was a decrease in MBP in CA1 (33%), CA3 (23%), and DG (25%) and synaptophysin in CA3 (61%) and an increase in GFAP in CA (490%), CA3 (380%), and DG (420%). In females, although there was an increase in MBP (410% in CA1) and synaptophysin (480% in DG) there was no change in neuronal density and GFAP.
Conclusion UPI results in decreased neuronal density within the hippocampus of IUGR male rats while not affecting females.
Speculation Neuronal development in the male rat hippocampus is more vulnerable to UPI-induced insult.
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