Role of nuclear receptors in fetal programming

核受体在胎儿编程中的作用

• 批准号: 357517-2008
• 负责人: Hardy, Daniel
• 金额: $ 1.82万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2008
• 资助国家: 加拿大
• 起止时间: 2008-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=403292
• 关键词: Role; nuclear; receptors; fetal; programming

The inverse relationship between birth weight and post partum health is one of the most fascinating discoveries in mammalian fetal biology. The principal hypothesis governing this relationship is that genetic and/or epigenetic changes underlie alterations in fetal development. Understanding the overall role of transcription factors in mediating these developmental events would provide us with a better understanding of the mechanisms controlling fetal development. In this proposal, we will use a 'candidate transcription factor' approach to first examine the role of one lipid-sensing nuclear receptor family member, the Liver X Receptor (LXR), involved in cholesterol clearance, in an intrauterine model of protein restriction in rats, which leads to lower birthweight, impaired offspring growth, decreased liver to body ratio, and an increase in fetal liver adiposity. With this unique model, we can examine for the first time the developmental changes in the in vivo interaction of transcription factors and epigenetic markers to target promoters, which play an important role in the coordinated control of gene transcription during fetal development.

出生体重和产后健康之间的反向关系是哺乳动物胎儿生物学中最引人入胜的发现之一。支配这种关系的主要假设是，遗传和/或表观遗传变化是胎儿发育变化的基础。了解转录因子在调节这些发育事件中的整体作用将为我们更好地理解控制胎儿发育的机制提供帮助。在这项研究中，我们将使用“候选转录因子”的方法，首先研究一个脂质敏感的核受体家族成员，肝脏X受体(LXR)，参与胆固醇清除，在蛋白质限制的大鼠宫内模型中的作用，该模型导致出生体重降低，后代生长受损，肝/体比降低，以及胎儿肝脏肥胖症的增加。有了这个独特的模型，我们可以第一次检查体内转录因子和表观遗传标记与靶启动子相互作用的发育变化，这在胎儿发育过程中基因转录的协调控制中发挥着重要作用。