TROPHOBLAST DIFFERENTIATION

滋养层分化

• 批准号: 3319025
• 负责人: MICHAEL J SOARES
• 金额: $ 16.39万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3319025
• 关键词: DNA replication; alkaline phosphatase; aminoacid analyzer; cell cycle; cell differentiation; cyclic AMP; decidua; developmental genetics; enzyme linked immunosorbent assay; enzyme mechanism; estrogens; extracellular matrix; gene expression; growth factor; high performance liquid chromatography; hormone regulation /control mechanism; immunocytochemistry; immunoprecipitation; in situ hybridization; laboratory mouse; laboratory rabbit; laboratory rat; nonmammalian vertebrate embryology; placenta; pregnancy; prenatal growth disorder; progesterone; prolactin; statistics /biometry; steroid hormone; tissue /cell culture; trophoblast

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.

绒毛膜尿囊胎盘在胎儿的发育中起着至关重要的作用 胎儿。 滋养层细胞，即胎盘的实质细胞，是 参与调节营养物质和废物之间的运输 母体和胎儿室，产生控制生长的激素 和母体和胎儿细胞的代谢，以及预防免疫学 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 有待阐明。 胎盘发育中断的后果可能是 明显导致终止妊娠或更微妙的结果 导致胎儿生长和成熟受损。 困难 伴随的胎儿发育与医疗保健的增加有关 产后需要。 该提案的目的是识别和表征细胞和 指导滋养层细胞分化的分子机制 并维持分化的滋养层表型。 分析 将主要关注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 与母体（子宫蜕膜）和胎儿的间质相互作用 起源。 这些相互作用影响胎盘的组织 它可以获取来自母体和胎儿环境的信号。 研究将利用正在发育的大鼠绒毛尿囊胎盘和细胞 从大鼠胎盘原基建立的系。 发育中的老鼠 绒毛膜尿囊胎盘是一个优秀的模型系统，因为它的反应 胎儿和母亲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）哪些因素导致功能和 大鼠绒毛膜尿囊胎盘区域的形态表型？ 2) 大鼠滋养层细胞系的起源是什么？ 他们代表？ 分子和免疫探针将用于 检查分化滋养层四种指标的表达 表型（胎盘催乳素-II、胎盘催乳素样蛋白-A、 P450scc和碱性磷酸酶）。将监测表达 在实验操作的滋养层中进行生化和组织学观察 细胞。 研究旨在评估细胞外基质的作用， 母体和胎儿因素、类固醇激素和环磷酸腺苷在指导中 滋养层细胞分化。 鉴定负责控制滋养层细胞的因素 差异化将显着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 容易受到病理破坏的发育阶段，因此， 治疗干预的潜在目标。