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

营养限制——胎盘和胎儿的大脑和肾脏的结果和机制

• 批准号: 8357664
• 负责人: PETER W. NATHANIELSZ
• 金额: $ 38.35万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357664
• 关键词: Address; Adult; Apoptosis; Brain; Cell physiology; Data; Development; Diabetes Mellitus; Diet; Eating; Elderly; Fetal Development; Funding; Goals; Grant; Growth; Growth and Development function; Health; Hypertension; Kidney; Life; Life Style; Morbidity - disease rate; Mothers; National Center for Research Resources; National Children' s Study; Nutrient; Obesity; Organ; Organism; Outcome; Papio; Perinatal Exposure; Placenta; Pregnancy; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Rodent; Secondary to; Sheep; Source; Staging; System; Time; United States National Institutes of Health; Uterus; angiogenesis; cost; detection of nutrient; experience; feeding; fetal; in utero; insight; maternal nutrient restriction; neonatal death; nephrogenesis; nonhuman primate; sex

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 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。