FETAL MEMBRANE CELL INTERACTIONS, ANATOMICAL RELATIONSHIPS, AND FUNCTIONS

胎儿膜细胞相互作用、解剖关系和功能

• 批准号: 6573856
• 负责人: JUDITH R HEAD
• 金额: $ 28.49万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6573856
• 关键词: amnion; amniotic fluid; birth; cell cell interaction; chemotaxis; collagen; confocal scanning microscopy; cytokine; electron microscopy; embryo /fetus membrane; gestational age; human tissue; immunocytochemistry; in situ hybridization; premature labor; protein structure; sex chromosomes; smoking; tobacco abuse

The long-range goal is to define morphological, structural, and functional interactions among cells of the fetal membranes that contribute to the maintenance of the physical integrity of this tissue. Selected studies of this project are coordinated with those designed to define the ontogeny of interstitial pro-collagen synthesis/processing in amnion. An alternative approach to most previous studies is proposed; viz, an investigation of the region of the fetal membranes most prone to rupture, i.e., the membranes immediately over the internal cervical os ("dependent" membranes) prior to membrane rupture. Focusing on the amnion, the cellular and structural changes that may be involved in spontaneous rupture during labor and those that may create greater vulnerability for premature rupture (PT-PROM) will be defined. The amnion is an important physical/physiological barrier. but in some pregnancies during labor, leukocytes migrate into and sometimes through the fetal membranes to accumulate in the amniotic fluid (AF). Yet, surprisingly little is known about this process, including the origin of the cells, and the route and mechanisms of transmigration. We propose 3 specific aims. The goal of Aim 1 is to define, by anatomical and morphological analyses, the changes in cells, cellular relationships, and collagen structure in the amnion of the dependent membranes during gestation by immunohistochemistry, electron microscopy, and confocal laser scanning microscopy applied to both conventional sections and whole tissue examined en face. The goal of Aim 2 is to conduct similar analyses of changes related to labor, and in pregnancies in which there is increased risk of premature rupture, viz., maternal smoking. The goal of Aim 3 is to define the origin of leukocytes with the fetal membranes and AF, the capacity of these cells to produce inflammatory cytokines, and the role of the amnion in providing the chemotactic signals that promote leukocyte migration. Leukocytes in AF and tissues from pregnancies with male fetuses will be analyzed for the Y chromosome by in situ hybridization. Chemotaxis assays will be conducted to define the capacity of amnion tissue and isolated cells to produce chemokines in response to relevant stimuli (IL-1, LPS, phagocytosis, cadmium, and hypoxia) and the ability of leukocytes to transmigrate amnion tissue under various conditions. The findings of these studies should provide important new information to clarify selected aspects of amnion function for which there are significant clinical implications.

远程目标是定义形态，结构和功能 胎儿膜细胞之间的相互作用，有助于 维持该组织的身体完整性。选定的研究 该项目与旨在定义的本体发育的项目协调 羊膜中的间质亲胶质合成/加工。另一种 提出了大多数先前研究的方法；即对 胎儿膜的区域最容易破裂，即 立即在内部宫颈OS上的膜（“依赖” 膜）在膜破裂之前。专注于羊膜 以及在自发破裂期间可能涉及的结构变化 劳动以及可能为早产造成更大脆弱性的劳动 将定义破裂（PT-PROM）。羊膜是重要的 物理/生理障碍。但是在分娩过程中的某些怀孕中， 白细胞迁移到胎儿膜中，有时迁移到 积聚在羊水（AF）中。然而，令人惊讶的是鲜为人知 关于此过程，包括单元格的起源，路线和 移民机制。我们提出了3个具体目标。目标的目标 1是通过解剖学和形态分析来定义的变化 细胞，细胞关系和胶原蛋白结构 免疫组织化学妊娠期间的依赖膜，电子 将显微镜和共聚焦激光扫描显微镜应用于两者 常规切片和整个组织都检查了面部。目标的目标 2是对与劳动有关的变化进行类似的分析，在 怀孕的怀孕增加了过早破裂的风险，即 孕产妇吸烟。目标3的目标是定义白细胞的起源 使用胎儿膜和AF，这些细胞产生的能力 炎性细胞因子，以及羊膜在提供的作用 促进白细胞迁移的趋化信号。 AF中的白细胞和 Y将分析与男性胎儿怀孕的组织 原位杂交染色体。趋化测定将进行 定义羊膜组织和分离细胞的能力产生 趋化因子响应相关刺激（IL-1，LPS，吞噬作用， 镉和缺氧）以及白细胞移民羊膜的能力 在各种条件下组织。这些研究的结果应该 提供重要的新信息以阐明羊膜的选定方面 具有重大临床意义的功能。