The Role of Leptin in Placental Development

瘦素在胎盘发育中的作用

基本信息

批准号：
8137077
负责人：
Laura Clamon SCHULZ
金额：
$ 24.17万
依托单位：
UNIVERSITY OF MISSOURI-COLUMBIA
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-05-15 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8137077
关键词：
Adipocytes Adult Affect Animals Barker Hypothesis Caloric Restriction Cardiovascular Diseases Cell Lineage Cells Complex Development Diet Embryo Environment Epigenetic Process Fetal Development Fetus Future Gene Expression Genes Genetic Giant Cells Goals Growth Factor Health Homeostasis Hormones Human Hypertension Inner Cell Mass Invaded Laboratories Leptin Life Style Lipids Long-Term Effects Mediating Mediator of activation protein Mentors Metabolic syndrome Methylation Morphology Mothers Mus Non-Insulin-Dependent Diabetes Mellitus Nutrient Nutritional Nutritional status Obesity Oocytes Organ Pathway interactions Phenotype Physiological Placenta Placentation Play Predisposition Pregnancy Process Proliferating Reproductive Biology Reproductive system Research Role Signal Transduction Stem cells Syncytiotrophoblast Syndrome Testing Time Work blastomere structure cell type critical period dietary restriction fetal food restriction implantation middle age mother nutrition nutrition obesity risk offspring preimplantation programs trophoblast wasting

项目摘要

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 origins of adult disease hypothesis posits that maternal nutrition during pregnancy has consequences for the future adult health ofthe fetus. In particular, it has been shown that severe caloric restriction during early pregnancy results in increased risk of obesity and cardiovascular disease when the affected fetus reaches middle age. The mechanisms by which this occurs are poorly understood, but the timing suggests that altered placental development may be involved. 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 ofthe effects of nutrition on placental development and subsequent adult health. The first specific aim is to determine whether leptin shortage mediates effects of nutrition on fetal and placental programming. Animals will be placed on a restricted diet with or without leptin replacement, and effects on placental development and adult adiposity determined. Placental size, morphology, gene expression, and gene methylation will be examined. In addition, the offspring of treated mothers will be followed through adulthood to determine longterm effects of diet and leptin replacement on obesity and lipid profiles. The second specific aim is to determine effects of leptin on placental differentiation at the cellular level. Trophoblast stem cells will be used to study the role of leptin in the differentiation of giant cell, syncytiotrophoblast cell, and spongiotrophoblast cell types. In addition to the scientific aims ofthe proposal, a goal of this "Pathways to Independence" project is to establish an independent laboratory in reproductive biology to pursue research on the effects of maternal environment on placental development.

胎盘发展是一个复杂的过程，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假定怀孕期间的产妇营养对胎儿的未来成人健康有影响。在特别是，已经表明，怀孕早期的严重热量限制会导致风险增加当受影响的胎儿达到中年时，肥胖和心血管疾病。这些机制发生这种情况的理解很少，但是时机表明胎盘发育的改变可能是涉及。该提议的基础假设是激素瘦素影响了多个步骤胎盘发展过程。瘦素是由脂肪细胞产生的，因此是潜在的介体营养对胎盘发育和随后的成人健康的影响。第一个具体目的是确定瘦素短缺是否介导营养对胎儿和胎盘编程的影响。动物如果有或没有瘦素替代，将放置在受限饮食中，对胎盘发育的影响并确定成人肥胖。胎盘大小，形态，基因表达和基因甲基化将是检查。此外，将遵循接受治疗的母亲的后代，以确定长期饮食和瘦素替代对肥胖和脂质谱的影响。第二个具体目的是确定瘦素对细胞水平胎盘分化的影响。滋养细胞干细胞将是用于研究瘦素在巨细胞分化中的作用海绵成素细胞类型。除了提案的科学目标外，该途径的目标是独立项目是建立一个独立的生殖生物学实验室来进行研究对孕产妇环境对胎盘发展的影响。