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

不孕不育是一个困扰英国许多家庭的问题，大约六分之一的夫妇去生育诊所就诊。然而，对许多患者来说，不孕的原因尚不清楚。通过提高我们对排卵过程中发生的分子过程（即从卵巢释放卵母细胞或卵子）的基本理解，我们希望有助于开发更有效的治疗不孕妇女的方法。我们的研究将集中在两种叫做TSG-6和i - α - 1的蛋白质上。我们已经知道，不能合成这两种蛋白质中的任何一种的老鼠不能产生可受精的卵母细胞。在哺乳动物的卵巢中，每个卵母细胞都包含在一个单独的卵泡中，在排卵前，卵母细胞被胶状物质包围。这种胶状物在卵母细胞从卵巢释放时起到保护作用，并提供一个大的表面积，帮助精子结合，这对受精至关重要。我们已经证明TSG-6和i - α - 1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坏，使卵母细胞释放。我们将使用各种方法进一步研究TSG-6和i - α - 1在排卵中的作用。例如，我们已经开发了分子工具，使我们能够（例如使用显微镜）精确地观察这些蛋白质在小鼠卵巢中的时间和位置，以及它们如何与其他分子结合在一起工作。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，但如果我们的结果与不孕治疗的发展有关，我们必须确定，我们认为对小鼠重要的任何过程也会发生在人类身上。一个新方法叫做？卵母细胞体外成熟？在英国，试管婴儿（IVM）刚刚开始用于治疗不孕妇女，它将允许我们使用治疗后留下的材料来测试这一点。这是曼彻斯特大学（University of Manchester）的研究人员与牛津生育中心（Oxford Fertility Unit）的临床医生之间的一个联合项目。曼彻斯特大学的研究人员在研究TSG-6和i - α - 1方面拥有多年经验，是该领域的世界领导者。这是英国第一个使用体外受精方法实现怀孕的中心。这两个小组的专业知识的结合为开展这项重要研究提供了一个独特的机会。

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.