Fetal Regulation of Placental Biology

胎盘生物学的胎儿调节

• 批准号: 6623501
• 负责人: NAMITA SAHGAL
• 金额: $ 12.6万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6623501
• 关键词: binding proteins; cell differentiation; cell line; disease /disorder etiology; embryo /fetus; embryo /fetus death; gene expression; genetically modified animals; glycogen; insulinlike growth factor; laboratory mouse; metabolism; placenta; placental transfer; prenatal growth disorder; stem cells; tissue /cell culture; trophoblast

DESCRIPTION (provided by applicant): Appropriate fetal growth and development is dependent upon a multitude of hormonal, genetic, environmental, and nutritional factors. Survival of the fetus is dependent on the ability of the placenta to maintain a balance between the adequate supply of nutrients and simultaneous disposal of waste materials to the maternal circulation. Hence, appropriate and rapid placental responses to insults in either the maternal or fetal compartments will significantly impact the outcome of the pregnancy. Acute fetal insult in the rodent results in changes in placental expression of various nutrient transporters, components of the insulin-like growth factor (IGF) signaling pathway, and the organization of a population of cells termed glycogen cells. Glycogen cells are an important indicator of normal placental development, and are frequently disrupted in pregnancies complicated by diabetes, preeclampsia and intrauterine growth retardation. Both IGF-I and IGF-II are known to have effects on fetal growth. IGF-II in addition has also been shown to play a significant role in placental growth, with IGF-II null animals developing small placentas with a dramatic depletion in glycogen cells. IGFs circulate bound to a family of insulin-like growth factor binding proteins (IGFBPs) which limit/modify their actions, along with displaying IGF-independent effects, unique to each IGFBP. The expression of one of these binding proteins, IGFBP-2 is remarkable, in that it is highly complementary to the expression of IGF-II throughout gestation. In this project we propose to investigate the effects of fetal insult on placental gene expression, and specifically the result of disruptions in the normal IGF-II - IGFBP-2 expression patterns in placental development. In Aim 1 we analyze changes in gene expression following fetal insult/death. Aim 2 focuses on placental development in animals with over expression of IGF-II and IGFBP-2. In Aim 3 the influence of IGF-II on the differentiation of the trophoblast cell lineage is examined. The proposed research utilizes both in vitro and in vivo strategies. Data derived from these experiments will add to our understanding of the factors involved in placental development, as well as of the role of the fetus in regulating placental metabolism to compensate for adverse fetal and maternal stimuli. This research will contribute to our knowledge of the etiology and pathogenesis of intrauterine growth retardation and perinatal morbidity and mortality.

描述（由申请人提供）：适当的胎儿生长和发育 取决于多种激素，遗传，环境， 营养因素。胎儿的存活取决于 胎盘维持平衡之间的营养供应充足， 同时将废物处理到母体循环中。因此，我们认为， 适当和快速的胎盘反应，无论是在母体或 胎儿间隔将显著影响妊娠的结果。 啮齿类动物中急性胎儿损伤导致胎盘表达的变化 各种营养转运蛋白，胰岛素样生长因子的成分 (IGF)信号通路，以及被称为 糖原细胞糖原细胞是胎盘正常的重要指标 发育，并经常在妊娠并发症中断， 糖尿病、先兆子痫和宫内发育迟缓。IGF-I和 已知IGF-II对胎儿生长有影响。IGF-II还 在胎盘生长中起重要作用，IGF-II无效 胎盘小的动物，糖原急剧减少 细胞胰岛素样生长因子与胰岛素样生长因子结合家族结合 限制/修饰其作用的蛋白质（IGFBPs），沿着显示 独立于IGF的效应，对每种IGFBP都是独一无二的。 其中一个的表达 结合蛋白，IGFBP-2是显着的，因为它是高度互补的， IGF-II在整个妊娠期的表达。在本项目中，我们建议 研究胎儿损伤对胎盘基因表达的影响， 特别是正常IGF-II - IGFBP-2破坏的结果 胎盘发育中的表达模式。 在目标1中，我们分析了 胎儿损伤/死亡后的基因表达。目标2关注胎盘 在IGF-II和IGFBP-2过表达的动物中的发育。在目标3 IGF-II对滋养层细胞系分化的影响 进行了检查。这项研究利用了体外和体内两种方法， 战略布局从这些实验中获得的数据将有助于我们了解 参与胎盘发育的因素，以及 调节胎盘对胎儿代谢的不利，以补偿胎儿 和母性刺激。这项研究将有助于我们了解 胎儿宫内发育迟缓的病因、发病机制及围生儿 发病率和死亡率。