The Role of Leptin in Placental Development

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，并可能 在怀孕期间受到母亲营养的影响。此外，成人疾病的胎儿起源假说 假设孕妇在怀孕期间的营养会对胎儿未来的成人健康产生影响。在……里面 特别是，已有研究表明，在怀孕早期严格限制卡路里会导致风险增加。 当受影响的胎儿达到中年时，肥胖和心血管疾病的风险就会增加。这些机制由 发生这种情况的原因尚不清楚，但时间安排表明，胎盘发育的改变可能是 牵涉其中。支持这一建议的假设是，激素瘦素影响大脑中的多个步骤 胎盘发育过程。瘦素是由脂肪细胞产生的，因此是一种潜在的 营养对胎盘发育和随后的成人健康的影响。第一个具体目标是 确定瘦素缺乏是否在营养对胎儿和胎盘编程的影响中起中介作用。动物 将被限制饮食，无论是否补充瘦素，以及对胎盘发育的影响 成年人的肥胖症被确定了。胎盘的大小、形态、基因表达和基因甲基化 检查过了。此外，接受治疗的母亲的后代将在整个成年期进行跟踪，以确定长期的情况。 饮食和瘦素替代对肥胖和血脂的影响。第二个具体目标是 从细胞水平确定瘦素对胎盘分化的影响。滋养层干细胞将成为 用于研究瘦素在巨细胞、合体滋养层细胞分化中的作用 海绵滋养层细胞类型。除了该提案的科学目标外，这一“途径”的一个目标 独立“计划是建立一个独立的生殖生物学实验室进行研究 母体环境对胎盘发育的影响。

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.