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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 次优的胎儿器官生长和发育是与新生儿死亡和长期发病率增加相关的主要问题。基本机制知之甚少。虽然主要原因是多种多样的，但胎儿发育不良通常继发于胎儿营养限制。啮齿动物和绵羊的研究提供了深入的了解，但平行的非人类灵长类动物的数据是最小的。 P01的总体目标是研究总体母体营养限制的影响：限制的母体进食70%的饲料，而自由进食对照（CTR）。我们假设，暴露于胎儿狒狒营养限制不利影响生长和关键细胞过程中的胎盘，胎儿大脑和肾脏。我们假设：30%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异性方式影响程序性细胞死亡。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：狒狒胎儿大脑发育;项目3  营养限制：狒狒胎儿肾脏发育。 我们使用一种独特的方法组合来评估母体营养对胎盘和胎儿大脑和肾脏发育的影响，这些器官是成人健康的关键器官。本P01解决了国家儿童研究目标。 哺乳动物生物体在子宫内发育期间比生命中的任何其他时间都要经历更多的里程碑。子宫内的次优条件会改变胎盘功能以及大脑和肾脏的发育。我们的研究将有助于确定子宫内经历的条件在以后的生活中易患高血压，肥胖和糖尿病的机制。 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.