The Role of Leptin in Placental Development

瘦素在胎盘发育中的作用

• 批准号: 7843384
• 负责人: Laura Clamon SCHULZ
• 金额: $ 25.16万
• 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 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7843384
• 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; Pre-Eclampsia; Predisposition; Pregnancy; Pregnancy Complications; 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

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。