Polycystic Ovary Syndrome (PCOS)
Polycystic Ovary Syndrome (PCOS) affects more than 5% of women of reproductive age and has a major impact both on fertility and on long-term health. It results in irregular menstruation, is the main reason for ovulation-related infertility and, because of its associated metabolic abnormalities, carries a high risk of developing diabetes. However we still know very little about its cause or causes, which makes diagnosis imprecise and means that we are treating the resulting symptoms rather than the underlying causes.
Our research focuses on how the ovaries function normally and on disorders of the ovary. For the last 15 years this work has been a collaboration between Stephen Franks and Kate Hardy. A major area of research is on the very common disorder of polycystic ovary syndrome (PCOS) that can lead to fertility problems and to problems with long-term health. Both Stephen and Kate are a world-leading figures in this important area.
In May 2015 we funded a new project by Stephen & Kate to help us understand the reasons why women with PCOS ovulate infrequently or not at all.
A woman is born with a supply of eggs that must last throughout her reproductive lifespan. These eggs are surrounded by a single layer of supporting (granulosa) cells and stored in tiny follicles in the ovary. This resting pool of follicles is termed the primordial pool. The processes that prompt primordial follicles to start growing remain unclear but there is evidence that locally produced growth factors play an important part, particularly those of the so-called transforming growth factor beta (TGFβ) family. TGFβ growth factors are proteins that are produced by and act in follicles of all sizes, including the very smallest, primordial, follicles.
In earlier studies of ovarian samples from women with PCOS, the team has shown that the problems that lead to infrequent ovulation may lie in the very earliest stages of the life of the ovarian follicle and they have already shown that at least one of the TGFβ family members (anti-Müllerian Hormone or AMH) is produced abnormally in very small follicles of women with PCOS.
Stephen and Kate will determine where and when (according to developmental stage) TGFβ growth factors (and their receptor targets) are produced, how they signal within ovarian cells, how they may interact other growth factor networks, and whether these processes differ between normal and polycystic ovaries. They expect these studies will provide important clues not only to understanding fertility problems in women with PCOS but also how they may relate to the development of metabolic disorders, including diabetes, to which these women are predisposed.