Fetal Brain Damage: A Placental Disorder

胎儿脑损伤：胎盘疾病

• 批准号: 7848643
• 负责人: ANNA A PENN
• 金额: $ 158.24万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7848643
• 关键词: Accounting; Affect; Anatomy; Animals; Autistic Disorder; Biology; Brain; Brain Injuries; Cerebral Palsy; Cessation of life; Communities; Development; Disease; Endocrine; Endocrine Glands; Fetal Development; Fetus; Functional disorder; Gene Expression; Goals; Hormones; Individual; Infant; Infection; Knowledge; Link; Molecular; Neurological outcome; Neuromodulator; Organ; Outcome; Oxytocin; Physiology; Placenta; Placenta Diseases; Placental Hormones; Pre-Eclampsia; Pregnancy; Premature Birth; Premature Infant; Premature Labor; Progestins; Renal function; Role; Schizophrenia; Secretin; Series; Shapes; System; Techniques; Testing; Time; United States; abstracting; developmental disease; fetal; high risk; improved; insight; neurodevelopment; novel strategies; premature; public health relevance; research study

DESCRIPTION (Provided by the applicant) Abstract: The placenta has long been underappreciated and understudied by the scientific community. Improper function of this critical organ causes fetal abnormalities, premature labor and the most common disease of pregnancy, preeclampsia. Despite the importance of the placenta, our understanding of its role in fetal development, especially at a molecular level, is crude. Sadly, our understanding of placental function may be compared to the knowledge of kidney function 50 years ago-- we can describe the anatomy, but not the biology. My overarching goal is to use new molecular techniques to understand placental function and its relationship to fetal outcomes. Here my specific goal is to investigate how placental hormones shape fetal brain development. As an endocrine organ, the placenta produces a wide array of neuroactive hormones. This endocrine function can be disrupted in many ways- by abnormal gene expression, infection, prematurity- resulting in long-term damage. Preterm birth, affecting one tenth of all deliveries, provides the most extreme case of hormone loss, but I hypothesize that it is just one of many cases in which placental dysfunction leads to brain damage. I will develop a series of animals in which individual hormones are specifically removed from the placenta at precise times during development. This system will allow the first direct, definitive tests of the placenta as a key regulator of fetal brain development. Both established hormones, such as progestins and oxytocin, and hormones that we have recently identified as neuromodulators made by the placenta, such as secretin, will be assessed. These experiments are likely to provide fundamental new insights in placental physiology and neurodevelopment, help redefine disorders such as cerebral palsy, autism and schizophrenia as disorders of the placenta and open new avenues to theraputic treatments to improve neurological outcome in fetuses and infants at high risk of developmental brain damage. Public Health Relevance: The placenta is a vital component of healthy pregnancy and compromised placental function has been linked to diverse developmental disorders including cerebral palsy, autism and schizophrenia. The early loss of placental hormones due to preterm birth, which affects more than 400,000 infants in the United States each year, and poor placental function due to preeclampsia or infection, which accounts for the majority of pregnancy-related deaths worldwide, may underlie these developmental disorders. Understanding the role of placental hormones during pregnancy and brain development, as investigated by the experiments proposed here, can provide new approaches to treatments that can improve outcome in preterm infants and others at high risk of developmental brain damage.

描述（申请人提供） 摘要：长期以来，胎盘一直被科学界所补充和研究。这种关键器官的功能不当会导致胎儿异常，过早劳动和最常见的怀孕疾病，先兆子痫。尽管胎盘很重要，但我们对其在胎儿发育中的作用，尤其是在分子水平上的理解是粗略的。可悲的是，我们对胎盘功能的理解可以与50年前的肾功能知识进行比较 - 我们可以描述解剖学，但不能描述生物学。我的总体目标是使用新的分子技术来了解胎盘功能及其与胎儿结果的关系。在这里，我的具体目标是研究胎盘激素如何塑造胎儿脑发育。作为内分泌器官，胎盘会产生各种神经活性激素。这种内分泌功能可以通过多种方式破坏 - 由于基因表达，感染，早产性异常，导致长期损害。早产，影响了所有分娩的十分之一，它提供了最极端的激素损失案例，但我假设这只是胎盘功能障碍导致脑损伤的许多情况之一。我将开发一系列动物，其中在发育过程中精确地从胎盘中专门从胎盘中特别去除单个动物。该系统将允许对胎盘作为胎儿脑发育的关键调节剂进行首次直接，确定的测试。两者都将评估我们最近确定为胎盘制造的神经调节剂的激素，例如孕激素，例如Sectrentin。这些实验可能在胎盘生理和神经发育方面提供基本的新见解，有助于重新定义诸如脑瘫，自闭症和精神分裂症等疾病，作为胎盘疾病，开放治疗的新途径，以改善胎儿的神经学结局，使胎儿中的神经学损害改善发育危害的风险。 公共卫生相关性：胎盘是健康怀孕的重要组成部分，胎盘功能受损与包括脑瘫，自闭症和精神分裂症在内的多种发育障碍有关。每年在美国的早产孕期影响40万名婴儿而引起的胎盘荷尔蒙的早期丧失，并且由于先兆子痫或感染而引起的胎盘功能较差，这是全世界大部分与怀孕有关的死亡，这可能是这些发育障碍的基础。如此处提出的实验所研究，了解胎盘激素在怀孕和大脑发育中的作用，可以提供新的治疗方法，这些方法可以改善早产儿和其他具有高发育性脑部损害风险的其他方法。