Director: Shyamal K. Roy, PhD
The current global population is close to 7 billion with over 78 million babies born each year. With approximately 33 million deaths per year, the population growth is approximately 45 million per year. The UN projects that the world population will reach just over 9.1 billion in 2050, challenging the world resources. On the other hand, approximately 11.8% of reproductive age women in the U.S.A. are infertile for various reasons. Infertility affects the psychological well-being of affected women and leads to social distress. Therefore, fertility management is absolutely critical. Because ovarian follicles, which are oocytes surrounded by cells called granulosa cells and the cal cells, are in the center of fertility, we seek to determine how follicle development occurs prior to ovulation in order to identify improved management, diagnosis and new therapies for human infertility, ovarian cancer and contraception. The long-term goal of my research is to improve the reproductive health of women by revealing the molecular underpinning of steroid hormones and growth factor regulation of ovarian follicular development from the primordial to the ovulatory stage and through the maturation of granulosa cells. My laboratory is focused on addressing how estrogen, the most important reproductive hormone in women, affects follicular development at two very critical steps in folliculogenesis.
Detailed Research Project Information
In project # 1, we study how estrogen, epidermal growth factor and transforming growth factor beta interact to bring about antral follicle development. Antral follicles are recruited by FSH for ovulation; hence, this transition step is critical for successful folliculogenesis and ovulation. We are investigating how classic estrogen receptor-b (ERb) mediates estrogen-induced proliferation of granulosa cells as well as induces ERa in the granulosa cells of immature ovarian follicles. Estrogen via ERa stimulates the expression of EGF-receptor and TGFB-receptor. We contend that once activated, these receptors initiate intracellular signals that lead to the maturation of granulosa cells within the ovarian follicle. This finely tuned process involves feedback control circuits between estrogen receptors and the growth factor receptors and is crucial for successful development of preovulatory follicles.
In project # 2, we focus on the mechanism of estrogen-mediated primordial follicle formation. Primordial follicles form the first cohort of follicles that determine the fecundity in mammalian females, including women. We contend that undifferentiated somatic cells in the ovary are transformed into epithelial granulosa cells by an estrogen-mediated PI3kinase signaling mechanism. We use a variety of molecular and cellular approaches to determine the morphogenesis of primordial follicles. The results may offer means to improve fertility in women, whose ovarian follicles do not respond to gonadotropins for whatever reason and also may provide new insight into the mechanisms of primordial follicle formation and development.