PLACENTAL PLASTICITY, FETAL GROWTH AND DEVELOPMENTAL PROGRAMMING

胎盘可塑性、胎儿生长和发育规划

• 批准号: 7958484
• 负责人: Peta Louise Grigsby
• 金额: $ 3.45万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-04 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958484
• 关键词: Adult; Affect; Amniotic Fluid; Animals; Biochemical; Biological Markers; Blood Circulation; Blood flow; Body Size; Candidate Disease Gene; Cardiovascular system; Cerebrum; Complement; Computer Retrieval of Information on Scientific Projects Database; Development; Disease; Environment; Fetal Growth; Funding; Gene Expression; Gene Family; Gestational Age; Glucose Transporter; Goals; Grant; Growth; Growth and Development function; Health; Individual; Inflammation Mediators; Institution; Interleukin-6; Lobe; Lung; Measurement; Metabolic Diseases; Modeling; Molecular; Molecular Profiling; Nutrient; Organ; Pathway interactions; Pattern; Placental Growth Factor; Placental Insufficiency; Plasma; Pregnancy; Primates; Reactive Oxygen Species; Research; Research Personnel; Resources; Risk; Source; Staging; Structure; Tumor Necrosis Factor-alpha; Ultrasonography; United States National Institutes of Health; Vascular Endothelial Growth Factors; Vascular blood supply; Work; fetal; hemodynamics; isoprostaglandin F2alpha type-III; nonhuman primate; offspring; postnatal; prenatal; programs

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. There is increasing evidence from epidemiologic and animal studies that a sub-optimal intrauterine environment is a key determinant of the postnatal health of individuals. Our working hypothesis is that a prenatal insult at critical stages of development produces varied effects on placental growth, structure and function through altered gene expression patterns, which modify fetal growth, organ development and the risk of adult disease. The goal of this project is to understand the mechanisms that regulate placental growth and development as well as the factors that "transmit" risk to the offspring for cardiovascular and metabolic diseases. Using a non-human primate model of placental insufficiency, we will characterize alterations in placental gene expression profiles (using a candidate gene approach as well as microarray analyses), after the vascular supply to the accessory placental lobe has been ligated at two different gestational ages. We will document plasma and amniotic fluid biomarkers for putative pathways responsible for compensatory placental growth. We will investigate several families of genes that are likely affected by placental growth mechanisms, including: i) Growth Regulating Factors (e.g., vascular endothelial growth factor, placental growth factor), ii) Inflammatory Mediators and Pro-oxidants (e.g.,interleukin-6, tumor necrosis factor-alpha and 8-isoprostane), and iii) Nutrient Transporters (e.g., glucose transporters). Molecular and biochemical studies will be complemented by serial ultrasound measurements to correlate fetal hemodynamics and changes in regional circulations (i.e., cerebral, pulmonary and placental blood flow), with fetal body size and proportions through pregnancy in order to understand the hemodynamic influences, which may regulate fetal growth.

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。 流行病学和动物研究越来越多的证据表明，次优的宫内环境是个体产后健康的关键决定因素。我们的工作假设是，在发育的关键阶段，产前损伤通过改变基因表达模式对胎盘的生长、结构和功能产生不同的影响，从而改变胎儿的生长、器官发育和成人疾病的风险。该项目的目标是了解调节胎盘生长和发育的机制以及将心血管和代谢疾病风险“传递”给后代的因素。使用非人灵长类动物模型的胎盘功能不全，我们将在胎盘基因表达谱的特征改变（使用候选基因的方法以及微阵列分析），血管供应后，副胎盘叶已被结扎在两个不同的胎龄。我们将记录血浆和羊水生物标志物的推定途径负责胎盘代偿性生长。我们将研究可能受胎盘生长机制影响的几个基因家族，包括：i）生长调节因子（例如，血管内皮生长因子，胎盘生长因子），ii）炎症介质和促氧化剂（例如，白细胞介素-6，肿瘤坏死因子-α和8-异前列烷），和iii）营养转运蛋白（例如，葡萄糖转运蛋白）。分子和生化研究将通过系列超声测量来补充，以将胎儿血流动力学和局部循环的变化（即，脑、肺和胎盘血流量），以及整个妊娠期间胎儿的身体大小和比例，以了解可能调节胎儿生长的血液动力学影响。