FUNCTIONAL CYTOLOGY OF THE PLACENTA AND FETAL MEMBRANES

胎盘和胎膜的功能细胞学

基本信息

批准号：
2196827
负责人：
GORDON C DOUGLAS
金额：
$ 18.37万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
1978
资助国家：
美国
起止时间：
1978-07-01 至 1999-03-31
项目状态：
已结题

项目摘要

The major long-term objective of these studies is to advance our understanding of placental development and function, particularly the cellular basis of trophoblast function. A critical event in trophoblast development is the differentiation of stem cell-like cytotrophoblast into the structurally and functionally mature syncytiotrophoblast. The central hypothesis of this proposal is that plasma membrane phospholipid (PL) metabolism plays a major role in trophoblast differentiation and function and that it is closely tied to the expression and function of cell surface adhesion molecules. This idea will be tested in three interrelated specific aims using the vitronectin receptor (VNR) as a model adhesion molecule. The studies take advantage of our ability to obtain pure cultures of cytotrophoblast and our ability to block or induce differentiation by manipulating culture conditions. Each aim is supported by preliminary data. Specific aim 1 examines the role of plasma membrane PL in trophoblast differentiation. Membrane PL content and asymmetry and the key metabolic pathways utilized by trophoblast will be examined. Anti- PL antibodies have been associated with recurrent pregnancy loss and it has been proposed hat they affect trophoblast differentiation. This hypothesis will be tested by examining the effects of aPL antibodies on normal trophoblast differentiation and function in vitro. Specific aim 2 explores the roles of VNR in trophoblast differentiation and function. The placenta is a rich source of this integrin but its role in trophoblast is not known. Changes in PL metabolism have been correlated with the attachment of cells to certain substrates and VNR activity is affected by membrane PL composition. VNR has also been implicated in cell fusion events. Its role in regulation of trophoblast differentiation and substrate attachment will be investigated and results correlated with the PL studies that comprise specific aim 1. Modulation of receptor expression by cytokines, growth factors and anti-PL antibodies will also be studied. Invasion of maternal spiral arteries suggest that an effective cell-cell adhesion system must exist to allow trophoblast cells to migrate along the endothelium. Little is known about trophoblast adhesion molecules, especially those mediating cell-cell adhesion. Specific aim 3 will characterize cell adhesion molecules involved in trophoblast-endothelial cell interaction in vitro and the effect of cytokines and aPL antibodies on this process. Together, the proposed studies should provide significant new information about cell membrane molecules that are critical to the regulation of trophoblast differentiation and function.

这些研究的主要长期目标是促进我们的了解胎盘发展和功能，特别是滋养细胞功能的细胞基础。滋养细胞中的关键事件发育是干细胞样细胞质细胞的分化结构和功能成熟的合成型成素细胞。中央该提议的假设是质膜磷脂（PL）代谢在滋养细胞分化和功能中起主要作用并且它与细胞表面的表达和功能紧密相关粘附分子。这个想法将在三个相互关联中测试使用玻染素受体（VNR）作为模型粘附的特定目的分子。研究利用我们获得纯净的能力细胞增生细胞的培养以及我们阻止或诱导的能力通过操纵培养条件的分化。每个目标都得到支持通过初步数据。特定目标1检查质膜的作用 PL在滋养细胞分化中。膜PL含量和不对称性和将检查由滋养细胞使用的关键代谢途径。反对- PL抗体与复发性妊娠丧失有关，IT 已经提出了帽子，它们会影响滋养细胞的分化。这假设将通过检查APL抗体对正常的滋养细胞分化和体外功能。具体目标2 探索VNR在滋养细胞分化和功能中的作用。这胎盘是该整合素的丰富来源，但其在滋养细胞中的作用是不知道。 PL代谢的变化与细胞附着在某些底物上，VNR活性受到影响膜PL组成。 VNR也与细胞融合有关事件。它在调节滋养细胞分化和将研究底物附件，结果与构成特定目标的PL研究1。受体表达的调节通过细胞因子，还将研究生长因子和抗PL抗体。母体螺旋动脉的侵袭表明有效的细胞细胞必须存在粘附系统，以允许滋养细胞沿着内皮。关于滋养细胞粘附分子知之甚少，特别是那些介导细胞粘附的人。具体的目标3将表征涉及滋养细胞内皮的细胞粘附分子细胞相互作用体外以及细胞因子和APL抗体的作用在此过程中。拟议的研究共同提供重要的研究有关细胞膜分子至关重要的细胞膜分子的新信息调节滋养细胞分化和功能。