Functional genomic analysis of the role of p53 in early embryo death after assisted reproductive technologies (ART).

p53 在辅助生殖技术 (ART) 后早期胚胎死亡中的作用的功能基因组分析。

• 批准号: nhmrc : 153703
• 负责人: Prof Christopher O'Neill
• 金额: $ 15.14万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/functional-genomic-analysis-technologies-art/96617
• 关键词: Functional; genomic; analysis; role; p53

Assisted reproductive technologies (ART, such as IVF and related techniques) are successful treatments for most forms of infertility. ART are expensive therapies and much of this cost is related to the relative inefficiency of the technology. Much of this is due to the high mortality of the resulting embryos. Typically, 45-80% of embryos produced by ART do not survive the first week. Consequently the chance of any individual embryo resulting in a successful birth is not high. There has been only modest increments in embryo survival in recent years. The low cahnce of individual embryos resulting in a baby means that: (1) generally several treatment cycles are required; (2) superovulation is used to maximise the number of embryos produced giving an accumulation of unwanted cryopreserved embryos; (3) more than one embryo is generally transferred resulting in a significant incidence of multiple pregancies. The high mortality of the early embryo seems to be a general feature of IVF but its causes and effectors are not known. It has recently been established that it largely occurs due to a form of cell 'suicide' known as apoptosis. This form of cell death has important normal functions: its activation allows for cells that are no longer required to be removed, allowing the remodelling of tissues and it also serves to remove cells that are irreversibly damaged. p53 is a protein that has the ability to 'sense' cell stress and damage and to direct the cell to undergo apoptosis if the stress is severe. This project will examine if ART cause increased expression of p53 and whether this elevation of p53 causes embryonic cell death. We will examine the factirs that control p53 expression in the embryo. using mice with mutations that stop the function of p53 and several of its regulatory proteins. Experiments will determine the susceptibility of embryos possessing these mutations and will therefore allow us to define the proteins causing apoptosis after ART.

辅助生殖技术（ART，例如 IVF 和相关技术）可以成功治疗大多数形式的不孕症。 ART 是一种昂贵的疗法，其中大部分成本与技术的相对低效有关。这很大程度上是由于所产生的胚胎的高死亡率。通常，45-80% ART 产生的胚胎在第一周就无法存活。因此，任何单个胚胎成功出生的机会并不高。近年来，胚胎存活率仅略有增加。单个胚胎产生婴儿的几率低意味着：（1）一般需要几个治疗周期； (2) 超排卵用于最大限度地增加产生的胚胎数量，从而积累不需要的冷冻胚胎； (3)通常移植多个胚胎，导致多胎妊娠的发生率很高。早期胚胎的高死亡率似乎是体外受精的普遍特征，但其原因和影响因素尚不清楚。最近已经确定，它主要是由于一种称为细胞凋亡的细胞“自杀”形式而发生的。这种形式的细胞死亡具有重要的正常功能：它的激活允许不再需要的细胞被去除，从而允许组织重塑，并且还可以去除受到不可逆损伤的细胞。 p53 是一种蛋白质，能够“感知”细胞压力和损伤，并在压力严重时引导细胞发生凋亡。该项目将检查 ART 是否会导致 p53 表达增加，以及 p53 表达增加是否会导致胚胎细胞死亡。我们将检查胚胎中控制 p53 表达的因素。使用具有停止 p53 及其几种调节蛋白功能的突变的小鼠。实验将确定具有这些突变的胚胎的易感性，从而使我们能够确定 ART 后引起细胞凋亡的蛋白质。