TROPHOBLAST DIFFERENTIATION

绒毛尿囊胎盘在胚胎发育中起着重要作用， 胎儿 滋养层细胞，胎盘的实质细胞， 参与调节营养物质和废物在 母体和胎儿间室，产生控制生长的激素， 和代谢的母体和胎儿细胞，并在预防免疫 排斥基因完全不同的胚胎 细胞和生化 控制滋养层细胞生长和分化的机制尚不清楚。 有待阐明。 胎盘发育中断的后果可能是 明显的导致怀孕的停止或更微妙的 导致胎儿生长和成熟受损。 困难 伴随着胎儿的发育， 产后需要。 该提案的目的是识别和表征细胞和 滋养层细胞分化的分子机制 和维持分化的滋养层表型。 分析 将主要集中在滋养层的内分泌分化 细胞 我们假设滋养层细胞的分化依赖于 在与母体（子宫蜕膜）和胎儿间质相互作用后， 起源 这些相互作用影响胎盘的组织， 它能接触到来自母体和胎儿环境的信号。 研究将利用发育中的大鼠绒毛尿囊胎盘和细胞 从大鼠胎盘原基建立的细胞系。 发育期大鼠 绒毛尿囊胎盘是一个很好的模型系统， 与胎儿和母体的相互作用很容易分离。 两大 以问题形式提出的具体目标将在 建议：1）哪些因素是负责的功能和 大鼠绒毛尿囊胎盘的形态表型？ 和2）大鼠滋养层细胞系的起源是什么， 他们代表？ 分子和免疫学探针将用于 检测分化滋养细胞的四项指标的表达， 表型（胎盘催乳素-II，胎盘催乳素样蛋白-A， P450 SCC和碱性磷酸酶）。 在实验操作的滋养层中， 细胞 研究旨在评估细胞外基质的作用， 母胎因素、类固醇激素和环磷酸腺苷在指导 滋养层细胞分化 滋养层细胞调控因子的鉴定 差异化将大大增加我们对一个基本的知识， 胚胎过程 此外，这些研究将允许识别 易受病理破坏的发育阶段，因此， 治疗干预的潜在目标。

The chorioallantoic placenta plays an essential role in the development of the fetus. Trophoblast cells, the parenchymal cells of the placenta, are involved in regulating the transport of nutrients and wastes between maternal and fetal compartments, producing hormones that control the growth and metabolism of maternal and fetal cells, and in preventing immunologic rejection of the genetically disparate embryo. Cellular and biochemical mechanisms controlling trophoblast cell growth and differentiation are yet to be elucidated. Consequences of disrupted placental development may be conspicuous resulting in the cessation of pregnancy or more subtle resulting in impaired fetal growth and maturation. Difficulties accompanying fetal development are associated with increased health care needs postnatally. The purpose of this proposal is to identify and characterize cellular and molecular mechanisms involved in directing trophoblast cell differentiation and in maintaining the differentiated trophoblast phenotype. The analysis will be largely focused on the endocrine differentiation of trophoblast cells. We hypothesize that trophoblast cell differentiation is dependent upon interactions with mesenchyme of maternal (uterine decidua) and fetal origin. These interactions influence the organization of the placenta and its access to signals emanating from maternal and fetal environments. Studies will utilize the developing rat chorioallantoic placenta and cell lines established from rat placental primordia. The developing rat chorioallantoic placenta is an excellent model system in that its responses to fetal and maternal interactions are readily dissociable. Two major specific aims presented in the form of questions will be addressed in the proposal: 1) What factors are responsible for the functional and morphological phenotypes of the zones of the rat chorioallantoic placenta? and 2) What is the origin of the rat trophoblast cell lines and what do they represent? Molecular and immunologic probes will be utilized to examine the expression of four measures of the differentiated trophoblast phenotype (placental lactogen-II, placental prolactin-like protein-A, P450scc, and alkaline phosphatase).Expression will be monitored biochemically and histologically in experimentally manipulated trophoblast cells. Studies are designed to evaluate roles of the extracellular matrix, maternal and fetal factors, steroid hormones and cyclic AMP in directing trophoblast cell differentiation. Identification of factors responsible for controlling trophoblast cell differentiation will significantly add to our knowledge of a fundamental embryologic process. Furthermore, these studies will permit identification of developmental stages susceptible to pathologic disruption and thus, potential targets for therapeutic intervention.