TROPHOBLAST DIFFERENTIATION

绒毛尿囊膜胎盘在胎盘发育中起重要作用 胎儿。滋养层细胞，胎盘的实质细胞，是 参与管理营养物质和废物之间的运输 母体和胎儿的隔间，产生控制生长的激素 以及母体和胎儿细胞的新陈代谢，以及在预防免疫学方面 排斥基因不同的胚胎。细胞和生化 控制滋养层细胞生长和分化的机制尚不清楚 有待澄清。胎盘发育受阻的后果可能是 明显的导致终止妊娠或更隐蔽的 导致胎儿发育和成熟受损。困难 伴随着胎儿的发育与增加的医疗保健有关 后天的需要。 这项提案的目的是识别和表征细胞和 调控滋养层细胞分化的分子机制 并维持滋养层细胞的分化表型。分析 将主要关注滋养层细胞的内分泌分化 细胞。我们假设滋养层细胞的分化依赖于 母体(子宫蜕膜)与胎儿间质的相互作用 起源。这些相互作用影响胎盘的组织和 它可以获得从母体和胎儿环境发出的信号。 研究将利用发育中的大鼠绒毛尿囊膜胎盘和细胞 从大鼠胎盘原基建立的系。发展中的速度 绒毛尿囊膜胎盘是一个很好的模型系统，因为它的反应 胎儿和母亲的相互作用很容易被分开。两大 以问题形式提出的具体目标将在 建议：1)哪些因素对功能和 大鼠尿囊膜胎盘区的形态表型？ 2)大鼠滋养层细胞系的来源是什么？ 他们代表了什么？分子和免疫学探针将被用于 检测分化滋养层细胞四种指标的表达 表型(胎盘催乳素-II、胎盘催乳素样蛋白-A、 P450scc和碱性磷酸酶)。表达将被监测 实验操作滋养层细胞的生化和组织学研究 细胞。研究旨在评估细胞外基质的作用， 母婴因素、类固醇激素和环磷酸腺苷在指导中的作用 滋养层细胞分化。 滋养层细胞调控因素的鉴定 差异化将显著增加我们对基本知识的了解 胚胎学过程。此外，这些研究将允许识别 易受病理性干扰的发育阶段，因此， 治疗干预的潜在靶点。

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.