Fetal growth restriction alters hippocampal 17-beta estradiol and estrogen receptor alpha levels in the newborn male rat

Fetal growth restriction (FGR) is associated with impaired neurodevelopmental outcomes in affected newborns. The pathogenesis of FGR-associated neurodevelopmental impairment implicates abnormal hippocampal function. The steroid hormone estrogen and its receptor, estrogen receptor alpha (ER alpha), are involved in the normal programming of hippocampal development and structure. However, the impact of FGR on hippocampal estrogen and hippocampal ER alpha is not well characterized. We hypothesized that FGR will reduce hippocampal and serum levels of 17-beta estradiol and its receptor, ER alpha, in the newborn rat hippocampus. We further hypothesize that FGR will reduce hippocampal ER alpha levels in a region-specific manner. To test our hypotheses, we used the well characterized rat model of FGR induced by uteroplacental-insufficiency in the pregnant Sprague-Dawley rat. Hippocampi and serum were obtained from FGR and control day 0 rat pups and examined for hippocampal 17-beta estradiol, serum 17-beta estradiol, and ER alpha mRNA and protein levels. Immunohistochemistry was performed to examine region-specific ER alpha staining. FGR decreased hippocampal 17-beta estradiol levels in the hippocampi of male newborn rats but not females. Serum 17-beta estradiol levels were not affected by FGR in either gender. FGR decreased hippocampal ER alpha mRNA levels in males but not females. Hippocampal ER alpha protein levels by Western blotting were not affected by FGR. However, FGR decreased apparent ER alpha staining in the cornu ammonis (CA) 1, CA3, and dentate gyrus regions in the hippocampi of male newborn rats but not females. We conclude that FGR affects the programming of hippocampal estrogen and hippocampal ER alpha levels in the newborn rat in a gender-specific manner.