The Role of Leptin in Placental Development

瘦素在胎盘发育中的作用

• 批准号: 7384640
• 负责人: Laura Clamon SCHULZ
• 金额: $ 9万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-15 至 2010-05-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7384640
• 关键词: Adipocytes; Adult; Affect; Animals; Barker Hypothesis; Biology; Cells; Complex; Development; Embryo; Environment; Fetus; Future; Gene Expression; Giant Cells; Goals; Grant; Health; Hormones; Human; Laboratories; Leptin; Localized; Mediating; Mediator of activation protein; Mentors; Obesity; Phase; Placentation; Pre-Eclampsia; Pregnancy Complications; Process; Reproductive Biology; Research; Role; Signal Pathway; Signal Transduction; Stem cells; Syncytiotrophoblast; Techniques; Training; cell type; dietary restriction; fetal; mother nutrition; nutrition; programs; research study; treatment effect; trophoblast

DESCRIPTION (provided by applicant): Placental development is a complex process that involves interactions among multiple cell types and may be affected by maternal nutrition during pregnancy. Further, the fetal origin of adult disease hypothesis posits that maternal nutrition during pregnancy has consequences for the future adult health of the fetus. The hypothesis underlying this proposal is that the hormone leptin influences multiple steps in the process of placental development. Leptin is produced by fat cells, and thus is a potential mediator of the effects of nutrition on placental development. In the mentored phase of this proposal, the first specific aim is to determine the role of leptin in trophoblast cell specification during preimplantation development. These experiments will localize leptin in the early embryo and determine whether the distribution of leptin is required for trophoblast cells to form. The second aim is to determine the mechanism of leptin-induced trophoblast invasiveness. These experiments will explore the cell signaling pathways and changes in gene expression that underlie leptin stimulation of trophoblast invasion. In the independent phase of this proposal, the first specific aim is to determine whether leptin mediates effects of nutrition on fetal and placental programming. Animals will be placed on a restricted diet with or without leptin treatment, and the effects on placental development and adult adiposity determined. The second specific aim is to determine effects of leptin on placental cell type differentiation. Trophoblast stem cells will be used to study the role of; leptin in the differentiation of giant cell, syncytiotrophoblast cell, and spongiotrophoblast cell types. My goal is to establish an independent laboratory in reproductive biology to pursue research on the effects of maternal environment on placental development. This grant would provide an opportunity for training in specific techniques and broader scientific questions in a leading laboratory in placental biology, and would allow me to pursue an independent line of research in this laboratory. The proposed project is relevant to human health in at least two ways. First, insufficient trophoblast invasion is associated with pre-eclampsia, the most common complication of pregnancy, and one which can be fatal. This project will examine one of the influences on trophoblast invasion. Second, this project will increase our understanding of the ways in which maternal nutrition during pregnancy, may influence placental development, and even adult health. ;

描述（由申请人提供）：胎盘发育是一个复杂的过程，涉及多种细胞类型之间的相互作用，并且可能会在怀孕期间受母性营养的影响。此外，成人疾病假设的胎儿起源表明，怀孕期间的母性营养对胎儿的未来成人健康有影响。该提议的基础假设是激素瘦素在胎盘发育过程中影响多个步骤。瘦素是由脂肪细胞产生的，因此是营养对胎盘发育影响的潜在介体。在该提案的指导阶段，第一个具体目的是确定瘦素在植入前发育过程中的滋养细胞细胞规范中的作用。这些实验将将瘦素定位在早期胚胎中，并确定是否需要瘦细胞形成瘦素的分布。第二个目的是确定瘦素诱导的滋养细胞侵入性的机制。这些实验将探索细胞信号通路和基因表达的变化，这是瘦素刺激滋养细胞侵袭的基础的变化。在本提案的独立阶段，第一个具体目的是确定瘦素是否介导营养对胎儿和胎盘编程的影响。有或没有瘦素治疗的情况下，动物将被置于受限饮食中，并确定对胎盘发育和成人肥胖的影响。第二个特定目的是确定瘦素对胎盘细胞类型分化的影响。滋养细胞干细胞将用于研究；在巨细胞分化，合成毒素细胞细胞和海绵素细胞类型的分化中的瘦素。我的目标是建立一个独立的生殖生物学实验室，以研究产妇环境对胎盘发展的影响。该赠款将为胎盘生物学领先的领先实验室中的特定技术和更广泛的科学问题提供培训的机会，并使我能够在该实验室进行独立的研究。拟议的项目与人类健康至少有两种方式相关。首先，滋养细胞的侵袭不足与先兆子痫，妊娠的最常见并发症以及可能致命的诱因有关。该项目将研究对滋养细胞入侵的影响之一。其次，该项目将提高我们对怀孕期间母亲营养，可能影响胎盘发展甚至成人健康的方式的理解。 ;