The Role of Leptin in Placental Development

瘦素在胎盘发育中的作用

• 批准号: 7620996
• 负责人: Laura Clamon SCHULZ
• 金额: $ 8.95万
• 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 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7620996
• 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; 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; preimplantation; 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，并且可能受到怀孕期间母体营养的影响。此外，成人疾病的胎儿起源假说认为，怀孕期间母亲的营养会对胎儿未来的成年健康产生影响。该提议的假设是，瘦素激素影响胎盘发育过程中的多个步骤。瘦素由脂肪细胞产生，因此是营养对胎盘发育影响的潜在介质。在该提案的指导阶段，第一个具体目标是确定瘦素在植入前发育过程中滋养层细胞规范中的作用。这些实验将在早期胚胎中定位瘦素，并确定瘦素的分布是否是滋养层细胞形成所必需的。第二个目的是确定瘦素诱导滋养层侵袭的机制。这些实验将探索瘦素刺激滋养层侵袭的细胞信号传导途径和基因表达的变化。在该提案的独立阶段，第一个具体目标是确定瘦素是否介导营养对胎儿和胎盘编程的影响。将在有或没有瘦素治疗的情况下对动物进行限制饮食，并确定对胎盘发育和成人肥胖的影响。第二个具体目标是确定瘦素对胎盘细胞类型分化的影响。滋养层干细胞将用于研究以下作用；瘦素在巨细胞、合体滋养层细胞和海绵滋养层细胞类型的分化中的作用。我的目标是建立一个独立的生殖生物学实验室，研究母体环境对胎盘发育的影响。这笔赠款将为胎盘生物学领先实验室提供特定技术和更广泛的科学问题培训的机会，并使我能够在该实验室进行独立的研究。拟议的项目至少在两个方面与人类健康相关。首先，滋养层侵袭不足与先兆子痫有关，先兆子痫是妊娠最常见的并发症，并且可能是致命的。该项目将研究对滋养层侵袭的影响之一。其次，该项目将加深我们对孕期母体营养可能影响胎盘发育甚至成人健康的了解。 ;

项目成果

Effect of food restriction and leptin supplementation on fetal programming in mice.

食物限制和瘦素补充对小鼠胎儿编程的影响。

• DOI: 10.1210/en.2012-1119
• 发表时间: 2012
• 期刊: Endocrinology
• 影响因子: 4.8
• 作者: Pennington,KathleenA;Harper,JenniferL;Sigafoos,AshleyN;Beffa,LindseyM;Carleton,StephanieM;Phillips,CharlotteL;Schulz,LauraC
• 通讯作者: Schulz,LauraC