The Astapova Lab is focused on the mechanisms of androgen actions in the ovary and ultimately improving the management of female fertility and ovarian hormone balance. While androgens are traditionally considered essential for male fertility, they are also critical regulators of ovarian function and fertility. In women, disorders of follicle development, specifically polycystic ovary syndrome (PCOS) and diminished ovarian reserve (DOR), contribute to the majority of cases of infertility. Disregulated androgen signaling has been implicated in both of these conditions: hyperandrogenemia is associated with excessive numbers of persistent antral follicles and anovulation in PCOS, while androgen deficiency is linked to accelerated follicle loss in DOR. Therefore, it is paramount to understand the mechanisms of androgen actions in the ovary in order to reduce the healthcare burden of androgen-related disorders in women.
Current research activity aims to investigate the non-coding transcriptional activity of androgen receptor in granulosa cells and the role of cytoplasmic adaptor protein paxillin in the ovary. Our working hypothesis is that androgens shift the microRNA expression profile of granulosa cells in the anti-apoptotic direction, resulting in increased survival of granulosa cells and follicle growth. In cases of androgen excess, such as in PCOS, this shift may interfere with the establishment of a dominant follicle and ovulation. We also believe that paxillin may be involved in this pathway upstream of the androgen receptor. Work by the Hammes Lab has shown that paxillin mediates non-genomic androgen signaling in prostate cancer, and we are evaluating similar mechanisms in granulosa cells. In fact, we have found that in granulosa cells, paxillin is necessary for androgen receptor protein expression. We have created a granulosa cell-specific paxillin knockout mouse model to better understand this pathway.