NUTRIENT RESTRICTION-PLACENTAL AND FETAL BRAIN AND RENAL OUTCOMES AND MECHANISMS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 胎儿器官生长发育不佳是导致新生儿死亡和长期发病率增加的主要问题。人们对潜在的机制知之甚少。虽然主要原因是多样的，但胎儿发育不良通常是胎儿营养限制的次要原因。啮齿动物和绵羊的研究提供了洞察力，但平行的非人类灵长类动物数据很少。 P01的总体目标是研究全球母亲营养限制的影响：受限制的母亲摄入70%由临时对照(CTR)食用的饲料。我们假设，暴露在营养限制下的胎儿狒狒会对胎盘、胎脑和肾脏的生长和关键细胞过程产生不利影响。我们假设：30%的全球母体营养限制1：损害生长；2：损害血管生成；3：影响IGF系统；4：改变细胞营养感知；5.以胎儿性别和发育阶段特有的方式影响细胞程序性死亡。这三个项目是：项目1营养限制：狒狒胎盘的生长和功能；项目2营养限制：胎儿猴脑发育；项目3营养限制：胎儿猴肾发育。 我们使用一种独特的方法组合来评估母亲营养对胎盘和胎儿大脑和肾脏发育的影响，这两个器官是成年人健康的关键器官。本P01涉及国家儿童学习目标。 哺乳动物有机体在子宫内发育过程中经历的里程碑比生命的任何其他时期都要多。子宫内的次优条件会改变胎盘功能以及脑和肾脏的发育。我们的研究将有助于确定在子宫中经历的状况在以后的生活中易患高血压、肥胖症和糖尿病的机制。临床医生将使用这些信息来了解怀孕期间的最佳生活方式和饮食。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Sub-optimal fetal organ growth and development are major problems associated with increased neonatal death and long-term morbidity. Underlying mechanisms are poorly understood. Whilst primary causes are diverse, poor fetal development is generally secondary to fetal nutrient restriction. Rodent and sheep studies provide insight but parallel nonhuman primate data are minimal. The overall P01 goal is to study effects of global maternal nutrient restriction: restricted mothers eat 70% feed eaten by ad lib controls (CTR). We hypothesize that exposure of fetal baboons to nutrient restriction adversely impacts growth and key cellular processes in placenta, fetal brain and kidney. We hypothesize: 30% global maternal nutrient restriction 1: impairs growth; 2: impairs angiogenesis; 3: impacts the IGF system; 4: alters cellular nutrient sensing; 5. influences programmed cell death, in a fetal sex and developmental stage specific manner. The three projects are: Project 1  Nutrient Restriction: Baboon Placental Growth and Function; Project 2  Nutrient Restriction: Fetal Baboon Brain Development; Project 3  Nutrient Restriction: Fetal Baboon Renal Development. We use a unique combination of approaches to evaluate maternal nutrient effects on development of placenta and fetal brain and kidney, key organs for adult health. This P01 addresses National Children's Study goals. The mammalian organism passes more milestones during in utero development than any other time of life. Sub-optimal conditions in utero alter placental function and brain and kidney development. Our studies will help determine mechanisms by which conditions experienced in the womb predispose to high blood pressure, obesity and diabetes in later life. Clinicians will use the information to understand optimal life style and diet in pregnancy.