Research Overview

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 female fertility. In women (or all people with ovaries), the majority of androgens are produced in the theca cells of the ovary, and are converted into estrogens by neighboring granulosa cells. One condition in which this balance is disrupted is polycystic ovary syndrome (PCOS), which affects up to 15% of reproductive age women and leads to infertility due to lack of ovulation, symptoms of excess androgen production, and abnormal ovarian follicle development. PCOS is strongly associated with metabolic syndrome, mood disorders and an increased risk of endometrial cancer.

Recently, we found that the cytoplalsmic adaptor protein paxillin increases androgen receptor expression in granulosa cells and may promote the negative effects of androgens in the ovary both in the contexts of PCOS and in age-related fertility decline. This may happen through cell membrane-initiated, non-genomic androgen actions. We are working to better understand how this plays a role in the ovary and whether paxillin may be a novel treatment target in PCOS. Our other current research aims to understand how systemic insulin resistance in PCOS affects ovarian function using a mouse model of PCOS. Our working hypothesis is that tissue-specific defects in insulin signaling expose the PCOS ovary to hyperstimulation by insulin, leading to disruptions in ovarian hormone production and follicle development.