The role of DHEA and androgens in the regulation of ovarian follicular development

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In the United Kingdom, 1 in 6 couples have fertility problems. Around a third of infertility in women is due to problems with ovulation (the monthly release of the egg). Before the egg is ready to be released, it develops inside a tiny fluid-filled space (called a follicle) on the ovary. Polycystic ovary syndrome (PCOS) is a condition in which women typically have an increased number of small follicles that do not develop properly; meaning ovulation does not take place. This is due to high levels of male hormones that cause a hormone imbalance. PCOS affects millions of women in the UK (5-10% of the women).Infertility in women is also linked to age, as the reserve of eggs in the ovaries gradually decreases. Elderly women typically have fewer follicles that develop poorly and ovulation does not occur. However, several studies have shown that treatment with male hormone increases fertility in women with low ovarian reserve. The biggest decrease in fertility begins during the mid thirties, when the male hormone production in the adrenal gland and the ovary decreases. Taken together, male hormones seem to play an important role in the development of the follicle and the egg, and thus potentially also in fertility.In my project I will study in detail the exact role of male hormones throughout the development of the follicle. Therefore I will culture mouse follicles and eggs. I will train to learn this technique from its developer, Professor Teresa Woodruff, in her laboratory in Chicago. I will carry out experiments exposing follicles to male hormones, in the laboratory of Professor Wiebke Arlt, who is a leading specialist on sex hormones at the University of Birmingham. Finally, I will correlate my findings in mouse follicles to human follicles. Through collaboration with the Birmingham Women's Hospital Fertility Centre, I will analyse follicular fluid from women undergoing in vitro fertilisation (IVF).I am convinced that my research will help to understand the mechanisms of infertility in women with PCOS and low ovarian reserve. I hope it will also lead to new fertility treatment options.