COMPARTMENTAL ANALYSIS OF PROTEOMIC BIOMARKERS DURING INTRA-UTERINE INFECTIONS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Our specific research aims focus upon defining the temporal and compartmental relationships among specific biomarkers and the biologic and clinical manifestations of early and late stages of ascending uterine infection (from choriodecidual to intra-amniotic models). Accumulating evidence indicates that intra-amniotic infection by genital mycoplasmas is a predominant cause of early preterm birth. The spatial and temporal characteristics of progressive stages of ascending infection and their relationship to biomarkers and antecedent signs of preterm labor have not been clearly defined in women. Similarly, previous animal models of intra-uterine infection have not taken into account that inflammatory responses in the decidua, fetal membranes and amniotic cavity may represent independent events that initiate different aspects of the preterm labor syndrome (e.g., premature cervical ripening, premature rupture of membranes, or uterine contractions). We demonstrated that choriodecidual inflammation with group B streptococcus is a transitional stage of ascending intra-uterine infection characterized by a graded response in amniotic fluid pro-inflammatory mediators, depending upon the presence or absence of bacteria in the amniotic fluid. Given the evidence for pre-implantation endometrial colonization with genital mycoplasmas, and their indolent natural history during pregnancy, ascending infection with ureaplasmas is likely to be quite different (i.e., time course or microbial characteristics, such as pathogenicity/virulence). The current proposal is expanding our understanding of the pathophyisology of choriodecidual inflammation/infection with Ureaplasma parvum in a non-human primate model and evaluating the spatial and temporal characteristics of progressive stages of ascending infection and their relationship to biomarkers and antecedent signs of preterm labor.