TROPHOBLAST DIFFERENTIATION

滋养层分化

• 批准号: 3319021
• 负责人: MICHAEL J SOARES
• 金额: $ 9.96万
• 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 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3319021
• 关键词: alkaline phosphatase; aminoacid analyzer; autoradiography; cell cycle; cell differentiation; developmental genetics; electrophoresis; gestational age; growth /development; growth factor; hormone regulation /control mechanism; nonmammalian vertebrate embryology; nucleic acid inhibitor; pregnancy; prenatal growth disorder; progesterone; prolactin; radiotracer; tissue /cell culture; trophoblast

The goals of our research program are to identify and understand cellular mechanisms involved in the regulation of placental development. Trophoblast cells are the functional unit of the placenta and their differentiation as gestation progresses is critical for the normal development of the fetus. The differentiation of trophoblast cells is characterized by an alteration in the cell cycle leading to an accumulation of DNA per cell. Nutritional deficiencies and drug abuse have pronounced effects on the development of the placenta and also on the fetus resulting in intrauterine growth retardation. It is presently not known how these environmental agents interfere with placental development. Experiments in Part 1 of this proposal are focused on the characterization of trophoblast differentiation. We are specifically interested in addressing two basic questions: 1) Are the patterns of trophoblast differentiation similar in vivo and in vitro? and 2) Do all trophoblast precursor cells possess the capacity to display the same type of differentiation in vitro? Part 2 of the research project is directed toward determining the involvement of DNA synthesis in the differentiation of trophoblast cells. Part 3 of the proposal is concerned with investigating the regulation of trophoblast differentiation by progesterone. Experiments are designed to examine the site, specificity and temporal characteristics of progesterone's actions. The proposed research relies extensively on analyzing the behavior of trophoblast cells in vitro and on the use of placental lactogen production as a functional, biochemical marker for trophoblast differentiation. Alkaline phosphatase activity and profiles of protein synthesis will also be assessed for their utility as markers for trophoblast differentiation. The experiments use cell culture, column chromatographic, electrophoretic, radioreceptor, and autoradiographic techniques to investigate trophoblast differentiation. The information garnered from these studies promises to advance our understanding of normal placental development and provide new insights regarding the susceptibility of this process to genetic and environmental modifications. Through our studies of trophoblast differentiation we will also generate significant data on the regulation of DNA synthesis and the cell cycle. The rat trophoblast giant cell potentially represents an important tool for studying the control of specific events during the cell cycle.

我们研究计划的目标是识别和理解细胞 参与胎盘发育调节的机制。 滋养层细胞是胎盘的功能单位及其 妊娠过程中的分化对于正常的发育至关重要 胎儿的发育。 滋养层细胞的分化是 其特征是细胞周期的改变导致积累 每个细胞的 DNA 数量。 营养缺乏和药物滥用已经很明显 对胎盘发育以及由此产生的胎儿的影响 在宫内生长迟缓。 目前尚不清楚这些 环境因素干扰胎盘发育。 实验于 该提案的第 1 部分重点关注滋养层的特征 差异化。 我们特别感兴趣的是解决两个基本问题 问题：1）滋养层分化的模式是否相似？ 体内和体外？ 2) 所有滋养层前体细胞都具有 是否有能力在体外表现出相同类型的分化？ 第 2 部分 该研究项目旨在确定 DNA 的参与 滋养层细胞分化过程中的合成。 第 3 部分 提案涉及调查滋养层的调节 通过黄体酮进行分化。 实验旨在检查 黄体酮作用的部位、特异性和时间特征。 拟议的研究广泛依赖于分析 体外滋养层细胞及其对胎盘催乳素产生的利用 作为滋养层分化的功能性生化标记。 碱性磷酸酶活性和蛋白质合成概况也将 评估它们作为滋养层分化标记的效用。 实验采用细胞培养、柱色谱、电泳、 放射受体和放射自显影技术来研究滋养层 差异化。 从这些研究中获得的信息有望 增进我们对正常胎盘发育的理解并提供新的 关于这一过程对遗传和基因的敏感性的见解 环境改造。 通过我们对滋养层的研究 差异化我们还将生成有关监管的重要数据 DNA 合成和细胞周期。 大鼠滋养层巨细胞 潜在地成为研究控制的重要工具 细胞周期中的特定事件。