Investigation of the roles of TSG-6 and inter-alpha-inhibitor in female fertility

TSG-6 和 inter-alpha 抑制剂在女性生育力中作用的研究

• 批准号: G0701180/1
• 负责人: Anthony Day
• 金额: $ 72.08万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0701180%2F1
• 关键词: Investigation; roles; TSG; inter; alpha

Infertility is an issue that affects many families in the UK, with around one in six couples attending fertility clinics. However, for many patients the cause of infertility is unclear. By improving our basic understanding of the molecular processes that occur during ovulation (i.e. the release of an oocyte (or egg) from the ovary) we hope to aid the development of more effective treatments for infertile women. Our research will focus on two proteins called TSG-6 and I-alpha-I. We already know that mice that do not synthesise either one of these proteins cannot produce oocytes that are fertilisable. In a mammalian ovary, each oocyte is contained in a separate follicle and before ovulation the oocyte becomes surrounded by a jelly-like substance. This jelly protects the oocyte during release from the ovary and provides a large surface area that aids sperm binding, which is essential for fertilisation. We have shown that both TSG-6 and I-alpha-I have critical roles in forming the jelly and now have new evidence suggesting that these proteins might also be involved in controlling the breakdown of the ovarian follicle wall to allow oocyte release. We will use various methods to further investigate TSG-6 and I-alpha-I in ovulation. For example, we have developed molecular tools that will allow us to look (e.g. using microscopy) at exactly when and where these proteins are present in mouse ovaries and how they might work together in association with other moelcules. Although studies on the mouse can tell us much about ovulation in general, if our results are to be relevant to the development of treatments for infertility, we must be certain that any processes we identify as being important in mice also occur in humans. A new method called ?in vitro maturation of oocytes?, or IVM, which is just beginning to be used to treat infertile women in the UK will allow us to test this, using material left over from treatments. This is a joint project between researchers at the University of Manchester, who have many years of experience in studying TSG-6 and I-alpha-I and are world-leaders in this field, and clinicians at the Oxford Fertility Unit ? the first centre in the UK to achieve pregnancies using the IVM procedure. The combination of expertise from these two groups represents a unique opportunity to carry out this important study.

不孕不育是一个影响英国许多家庭的问题，大约六分之一的夫妇参加生育诊所。然而，对于许多患者来说，不孕症的原因尚不清楚。通过提高我们对排卵过程中发生的分子过程（即卵母细胞（或卵子）从卵巢中释放）的基本理解，我们希望帮助开发更有效的不孕妇女治疗方法。我们的研究将集中在两种名为TSG-6和I-alpha-I的蛋白质上。我们已经知道，不合成这两种蛋白质的小鼠不能产生可受精的卵母细胞。在哺乳动物的卵巢中，每个卵母细胞包含在一个单独的卵泡中，在排卵前卵母细胞被一种类似卵泡的物质包围。这种胶状物在卵母细胞从卵巢释放的过程中保护卵母细胞，并提供一个大的表面积，有助于精子结合，这对受精至关重要。我们已经证明，TSG-6和I-alpha-I在形成果冻中起着关键作用，现在有新的证据表明，这些蛋白质也可能参与控制卵泡壁的破裂，以允许卵母细胞释放。我们将采用各种方法进一步研究TSG-6和I-α-I在排卵中的作用。例如，我们已经开发出分子工具，使我们能够准确地观察（例如使用显微镜）这些蛋白质何时何地存在于小鼠卵巢中，以及它们如何与其他分子一起工作。虽然对小鼠的研究可以告诉我们很多关于排卵的一般情况，如果我们的结果与不孕症治疗的发展有关，我们必须确定我们认为在小鼠中重要的任何过程也发生在人类中。一种新的方法叫做？卵母细胞的体外成熟，或IVM，在英国刚刚开始用于治疗不孕妇女，将使我们能够测试这一点，使用治疗后留下的材料。这是曼彻斯特大学的研究人员与牛津生育中心的临床医生之间的联合项目，他们在研究TSG-6和I-alpha-I方面有多年的经验，是该领域的世界领导者。这是英国第一个使用IVM程序实现怀孕的中心。这两个小组的专门知识相结合，为开展这项重要研究提供了一个独特的机会。