Decidua and Fetal Membranes as a Paracrine System

蜕膜和胎儿膜作为旁分泌系统

• 批准号: 6896602
• 负责人: Gillian Doreen Bryant-Greenwood
• 金额: $ 30.67万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6896602
• 关键词: Macaca mulatta; amnion; cell line; clinical research; decidua; embryo /fetus membrane; enzyme linked immunosorbent assay; extracellular matrix; female; gene expression; hormone regulation /control mechanism; human subject; injury; injury /disease stressor; paracrine; polymerase chain reaction; pregnancy disorder; premature labor; relaxin; tissue /cell culture; uterus

DESCRIPTION (provided by applicant): Preterm birth is not only the major cause of infant mortality, but also places the surviving individual at increased risk for significant mental and physical disabilities and major adult diseases. The preterm premature rupture of the fetal membranes (PPROM) is the cause of 30-40% of all preterm births and about 40% of these are due to infection. We have identified the only non-infectious pathway for PPROM to date. In these women with PPROM and no infection, there is increased expression of the relaxin genes and proteins in the decidua and placenta. Relaxin causes increased growth of the fetal membranes via stimulation of IGF-ll and increased degradation of the extracellular matrix (ECM). We have measured 488 genes in rare PPROM tissues, devoid of many of the usual confounding variables associated with preterm birth and shown relaxin and the expression of 29 other genes altered. From these data, three sets of genes/gene pathways have been chosen for further study: a pathway for development/growth, an inflammatory pathway and two genes whose products alter the structure of the ECM. We will place relaxin into the context of these changes, in order to understand this pathology further. Thus, in Specific Aim 1, we will study the relationships of relaxin to the genes/pathways altered at PPROM, in cell lines, tissue explants and in vivo. In Specific Aim 2, we will carry out a collaborative study using a rhesus monkey model and give relaxin directly into the amniotic cavity at preterm. The structure of the membranes and the genes/pathways of interest will be studied. In Specific Aim 3, an in vitro model will be used to study the effects of the rupture on the tissue. This will allow us to distinguish the cause of PPROM from its effect. These changes will then be sought after PPROM in vivo. The combined results will significantly increase our understanding of the non-infectious cause(s) of PPROM.

描述（由申请人提供）：早产不仅是婴儿死亡率的主要原因，而且还使幸存的人面临着严重的精神和身体残疾和主要成人疾病的风险。胎儿膜的早产过早破裂（PPROM）是所有早产出生的30-40％的原因，其中约40％是由于感染。我们已经确定了迄今为止PPROM的唯一非感染途径。在这些患有PPROM且无感染的女性中，在Decidua和胎盘中，松弛素基因和蛋白质的表达增加。松弛素通过刺激IGF-LL和细胞外基质（ECM）降解而导致胎儿膜的生长增加。 我们已经测量了稀有PPOM组织中的488个基因，这些基因没有许多与早产相关的常规混杂变量，并显示出松弛素和其他29个其他基因的表达。从这些数据中，已经选择了三组基因/基因途径进行进一步研究：开发/生长的途径，炎症途径和两个基因，其产物改变了ECM的结构。为了进一步了解这种病理，我们将把放松素放在这些变化的背景下。因此，在特定的目标1中，我们将研究松弛素与PPROM，细胞系，组织外植体和体内改变的基因/途径的关系。在特定的目标2中，我们将使用恒河猴模型进行协作研究，并直接将松弛蛋白放入早产的羊水腔。将研究膜和感兴趣的基因/途径的结构。在特定的目标3中，将使用体外模型来研究破裂对组织的影响。这将使我们能够区分PPROM的原因。然后将在体内寻求这些变化。结合的结果将大大增加我们对PPROM非感染原因的理解。