The Special Emphasis Research Career Award is awarded to develop capabilities in fundamental, applied, and/or clinical research. The purpose of this project was to develop a well-characterized rhesus monkey model of pregnancy with emphasis on pathologic changes in placental tissues seen in different modes of delivery. Non-SIV-infected rhesus monkeys, were used to determine the effects of preterm and term cesarean delivery on the maintanance or loss of placental integrity. 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. Five cases in each group have been evaluated at this time and the following results were found. 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 aproximately 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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000164-35
Application #
5219851
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
35
Fiscal Year
1996
Total Cost
Indirect Cost
Mahalingam, Ravi; Kaufer, Benedikt B; Ouwendijk, Werner J D et al. (2018) Attenuation of Simian Varicella Virus Infection by Enhanced Green Fluorescent Protein in Rhesus Macaques. J Virol 92:
Kumar, Vinay; Mansfield, Joshua; Fan, Rong et al. (2018) miR-130a and miR-212 Disrupt the Intestinal Epithelial Barrier through Modulation of PPAR? and Occludin Expression in Chronic Simian Immunodeficiency Virus-Infected Rhesus Macaques. J Immunol 200:2677-2689
Parthasarathy, Geetha; Philipp, Mario T (2018) Intracellular TLR7 is activated in human oligodendrocytes in response to Borrelia burgdorferi exposure. Neurosci Lett 671:38-42
McNamara, Ryan P; Costantini, Lindsey M; Myers, T Alix et al. (2018) Nef Secretion into Extracellular Vesicles or Exosomes Is Conserved across Human and Simian Immunodeficiency Viruses. MBio 9:
Yi, Fei; Guo, Jia; Dabbagh, Deemah et al. (2017) Discovery of Novel Small-Molecule Inhibitors of LIM Domain Kinase for Inhibiting HIV-1. J Virol 91:
Jorgensen, Matthew J; Lambert, Kelsey R; Breaux, Sarah D et al. (2017) Pair housing of Vervets/African Green Monkeys for biomedical research. Am J Primatol 79:1-10
Ramesh, Geeta; Martinez, Alejandra N; Martin, Dale S et al. (2017) Effects of dexamethasone and meloxicam on Borrelia burgdorferi-induced inflammation in glial and neuronal cells of the central nervous system. J Neuroinflammation 14:28
Parthasarathy, Geetha; Philipp, Mario T (2017) Receptor tyrosine kinases play a significant role in human oligodendrocyte inflammation and cell death associated with the Lyme disease bacterium Borrelia burgdorferi. J Neuroinflammation 14:110
Calenda, Giulia; Villegas, Guillermo; Barnable, Patrick et al. (2017) MZC Gel Inhibits SHIV-RT and HSV-2 in Macaque Vaginal Mucosa and SHIV-RT in Rectal Mucosa. J Acquir Immune Defic Syndr 74:e67-e74
Datta, Dibyadyuti; Bansal, Geetha P; Grasperge, Brooke et al. (2017) Comparative functional potency of DNA vaccines encoding Plasmodium falciparum transmission blocking target antigens Pfs48/45 and Pfs25 administered alone or in combination by in vivo electroporation in rhesus macaques. Vaccine 35:7049-7056

Showing the most recent 10 out of 352 publications