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

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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.