Molecular Reproductive Endocrinology Laboratory

Olson Center for Women's Health
Department of Obstetrics & Gynecology

Director
Shyamal K. Roy, Ph.D.

Estrogen is a female reproductive hormone that regulates a variety of physiological processes. Evidence indicates that estrogen stimulates the multiplication of granulosa cells that are present in ovarian follicles, and regulates their functions. However, the mechanisms underlying the estrogen effects on granulosa cell functions remain unclear. Similarly, despite sporadic information, the role of estrogen in regulating primordial follicle formation in mammals is not clearly understood. Primordial follicles represent a finite pool of early follicles that provide follicles for ovulation throughout the reproductive life of a female. A significant number of primordial follicles die during ovary development, and an early depletion of this pool leads to premature ovarian failure, and infertility due to ovarian causes. Therefore, understanding the factors regulating the formation and development of primordial follicles and the mechanisms of such regulation may lead to improved therapeutic management of infertility.

The focus of my laboratory is to determine (1) the role of estradiol-17b on granulosa cell differentiation, and (2) the mechanisms of primordial follicle formation and development. Our studies during the past decade have revealed the role of EGF and TGFb in controlling granulosa cell proliferation. We use hamsters because human and hamster follicular response to regulatory factors is similar, and to obtain information that can be applied to human follicles in culture. Unless we clearly know the hierarchy of different factors in the regulatory cascade and their potential interaction during follicular development, endocrine manipulation of the ovary will be a hit or miss approach. We have determined that classic estrogen receptors, such as ESR1 and ESR2, are expressed differentially in the granulosa cells as follicles are recruited for ovulation. Interestingly, this unique ESR expression correlates with the upregulation of EGFR in granulosa cells, especially those express the LH-receptor. Now we are examining the cause and effect relationship between ESR and EGFR expression with reference to granulosa cell differentiation. In this context, we also use human granulosa cells that are obtained from routine IVF procedure.

The second focus of my laboratory is to determine the factors regulating and the mechanisms of somatic cell differentiation into primordial granulosa cells during early ovarian morphogenesis.  Our studies have so far indicated that estrogen plays a profound role in somatic cell differentiation. Further, bone morphogenetic proteins (BMPs) appear to be significantly involved in this process. We are examining the relationship between the estrogen and BMPs in ovarian somatic cell differentiation.

The results may offer means to improve fertility in women, whose ovarian follicles do not respond to gonadotropins for whatever reasons, and also may provide new insights into the mechanisms of primordial follicle formation and development.

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Date last updated: November 29, 2007