The Special Emphasis Research Career Award (SERCA) is awarded to develop capabilities in fundamental, applied, and/or clinical research. The last 2 years of this SERCA are concerned with development of a well characterized rhesus monkey model of pregnancy with emphasis on pathologic changes in placental tissues seen in different modes of delivery. The goal of this study, utilizing non-SIV-infected rhesus monkeys, is to determine the effects of preterm and term cesarean delivery on the maintenance or loss of placental integrity. In previous studies utilizing SIV-infected rhesus, the role of SIV and mode of delivery could not be adequately evaluated in terms of their separate effects on the placenta. The role of cesarean delivery, as a means of preventing the vertical transmission of HIV, is being addressed in human studies. Determination of the normal changes"""""""" expected in placental tissue will allow future utilization of this model for testing biolologic and chemotherapeutic agents and their effects on the placenta. Thirty rhesus pregnancies were monitored by ultrasound and blood samples were collected from the dams for hematology and lymphocyte subset determination. The infants were delivered by either vaginal, 10 day preterm cesarean, or elective term cesarean surgery and placental tissues were collected for evaluation. The frequency and severity of lesions is similar in placentae delivered vaginally and by term cesarean sections, while preterm cesarean delivered placentae had the lowest overall incidence and severity of lesions. Mild to moderate inflammatory cell infiltrates and necrosis occur to a similar degree in the decidua basalis and basal plate in all modes of delivery. Inflammatory cells within the trophoblastic shell, intervillus space, villi, infarcts, chorionic plate and fetal vessels occur to a similar degree in term cesarean and vaginal deliveries but are significantly decreased (by about 1/2) in preterm deliveries. The frequency and size of marginal, basal, and central infarcts is decreased in preterm cesarean deliveries when compared to vaginal and term cesarean deliveries. Of all parameters examined, inflammation of the decidua vera and chorion was most dramatically reduced in the preterm cesarean group when compared to the other 2 groups. No inflammatory cells were observed in the chorion and membrane of the preterm delivered placentae. In the decidua vera, mononuclear cells were decreased by 50% and neutrophils were decreased by 90%. All hematologic parameters remained within normal limits throughout pregnancy. However, there was a tendancy for RBC and hematocrit to decline, segmented neutrophils to decrease and lymphocytes to increase. Platelets tended to decline until approximately 150 days gestation and then increased slightly, but never regained 1st trimester levels. Flow cytometry results indicated CD8+ cells increased while CD4+ cells remained stable, leading to a decline in the CD4+/CD8+ ratio. This was most apparent during the last 2 weeks of gestation. Throughout gestation, the percent of helper-inducer cells (%CD4+CD29+/total %CD4+) increased while there was a decline in B cells, with term levels falling to less than 1/2 of initial values. The dams, infants, and placentas in this study have served as controls for a pilot study of Plasmodium-infected pregnant rhesus monkeys. This study provided control data necessary for the evaluation of fetal growth and development, the identification of significant clinical changes in the mothers, the characterization of Plasmodium-induced lesions in the placenta, and infant evaluations.
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