COMPARTMENTAL ANALYSIS OF PROTEOMIC BIOMARKERS DURING INTRA-UTERINE INFECTIONS

子宫内感染期间蛋白质组生物标志物的区室分析

• 批准号: 8357791
• 负责人: Peta Louise Grigsby
• 金额: $ 5.82万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357791
• 关键词: Accounting; Amniotic Fluid; Animal Model; Bacteria; Biological Markers; Cervical Ripening; Characteristics; Clinical; Decidua; Endometrial; Event; Fetal Membranes; Funding; Genital system; Grant; Indolent; Infection; Inflammation; Inflammation Mediators; Inflammatory Response; Modeling; Mycoplasma; National Center for Research Resources; Natural History; Pathogenicity; Pregnancy; Premature Birth; Premature Labor; Premature Rupture Fetal Membranes; Primates; Principal Investigator; Proteomics; Research; Research Infrastructure; Resources; Source; Staging; Streptococcus Group B; Syndrome; Time; United States National Institutes of Health; Ureaplasma; Ureaplasma urealyticum biovar 1; Uterine Contraction; Virulence; Woman; amniotic cavity; cost; intraamniotic infection; microbial; nonhuman primate; preimplantation; premature; response

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.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 我们的具体研究目标集中在定义特定生物标志物之间的时间和房室关系以及上行性子宫感染早期和晚期的生物学和临床表现（从绒毛膜蜕膜到羊膜内模型）。越来越多的证据表明，生殖道支原体的羊膜内感染是早期早产的主要原因。上行感染进展阶段的时空特征及其与生物标志物和早产先兆的关系在女性中尚未明确定义。类似地，先前的宫内感染动物模型没有考虑到蜕膜、胎膜和羊膜腔中的炎症反应可能代表引发早产综合征不同方面的独立事件（例如，子宫颈过早成熟、胎膜早破或子宫收缩）。我们证明了B组链球菌引起的绒毛膜蜕膜炎症是上行性宫内感染的过渡阶段，其特征是羊水促炎介质的分级反应，取决于羊水中是否存在细菌。考虑到生殖器支原体在着床前子宫内膜定植的证据，以及它们在妊娠期间的惰性自然史，支原体的上行感染可能非常不同（即，时间进程或微生物特征，如致病性/毒力）。目前的建议是扩大我们的了解绒毛膜蜕膜炎症/感染的非人灵长类动物模型中的微小脲原体的病理生理学和评估的空间和时间特征的渐进阶段的上升感染和它们的关系的生物标志物和先兆早产的迹象。