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

在英国，每6对夫妇中就有一对有生育问题。女性中约三分之一的不孕症是由于排卵问题(每月卵子的释放)。在卵子准备释放之前，它会在卵巢上一个充满液体的微小空间(称为卵泡)内发育。多囊卵巢综合征(PCOS)是一种女性通常会有更多的小卵泡不能正常发育的情况，这意味着不会排卵。这是由于男性荷尔蒙水平过高，导致荷尔蒙失衡。多囊卵巢综合征影响英国数百万女性(占女性的5%-10%)。女性不孕不育也与年龄有关，因为卵巢中的卵子储备逐渐减少。老年妇女通常较少发育不良的卵泡，不会排卵。然而，几项研究表明，男性激素治疗可以提高卵巢储备不足女性的生育力。生育力最大的下降开始于35岁左右，此时肾上腺和卵巢中的雄性激素分泌减少。总而言之，男性激素似乎在卵泡和卵子的发育中发挥着重要作用，因此也可能在生育方面发挥重要作用。在我的项目中，我将详细研究男性激素在卵泡发育过程中的确切作用。因此，我将培养小鼠的卵泡和卵子。我将在芝加哥的实验室里接受培训，从它的开发者特蕾莎·伍德拉夫教授那里学习这项技术。我将在伯明翰大学领先的性激素专家Wiebke Arlt教授的实验室里进行让卵泡接触男性激素的实验。最后，我将把我在小鼠卵泡中的发现与人类卵泡联系起来。通过与伯明翰妇女医院生育中心的合作，我将分析接受体外受精(IVF)的妇女的卵泡液。我相信我的研究将有助于了解患有多囊卵巢综合征和卵巢储备不足的妇女的不孕机制。我希望这也会带来新的生育治疗选择。

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.