Grant: Project Grant

The processes of ovulation and consequent formation of the corpus luteum are essential for providing the gamete for fertilization, for transport of the embryo to the uterus and for implantation and successful gestation. We are studying the events surrounding the ovulatory process to learn the mechanisms by which ovulation occurs and the resulting corpus luteum is formed. The focus of the investigation is two closely related nuclear receptors known as steroidogenic factor-1 (Sf-1, Nr5a1) and liver receptor homolog-1 (Lrh-1, Nr5a2), that are essential to ovulation and luteal formation. The first objective is to employ novel mouse models of ovary specific deletion of these factors. The second objective is to develop an integrative or systems understanding of the role of both elements in the ovulatory process by employing new methods to determine the global gene expression changes that occur during ovulation, and to establish the role of Sf-1 and Lrh1-1 in their regulation. The third goal is to address the mechanisms by which Lrh-1 modifies transcriptional events via cofactors to induce the multiple changes in ovarian somatic cells. The fourth goal is to explore the expression of Lrh-1 and Sf-1 and their targets in ovarian cells from infertile patients to better understand ovarian dysfunction.