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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objectives of this research and career development grant are to utilize a nonhuman primate experimental model of intra-uterine infection with Ureaplasma parvum to characterize the temporal and mechanistic interactions among biomarker expression profiles (i.e., IGFBP-1 proteolytic fragments, calgranulins A and B and annexin II), in maternal and fetal compartments at defined stages of ascending uterine infection (from choriodecidual to intra-amniotic models). It is our hypothesis that specific biomarker profiles (spatial and temporal characteristics), will serve as surrogates for the stage of progression of ascending intra-uterine infection. An important aspect of this study is to determine the fetal physiologic adaptations to intra-amniotic infection (i.e., endocrine status, respiratory parameters and hemodynamic changes in regional and placental circulations), and to assess the efficacy of a combined therapeutic approach for improving fetal cardio-respiratory homeostasis. The work proposed is unique in its combined use of diagnostic and interventional strategies in a nonhuman primate model of intra-uterine infection (experimental choriodecidual and intra-amniotic stages). It is our expectation that the results of these studies will advance clinical management and facilitate the early diagnosis of women that are at risk for preterm delivery as a consequence of intra-uterine infection.