Grant: Project Grant

Infertility affects some 12-15 % of couples of reproductive age in developed countries, and some 186 million people worldwide. Two major issues have been identified, the first being depletion of the ovarian reserve of primordial follicles resulting in premature ovarian failure. The second is disorders in ovulation. The lack of understanding of the mechanisms of infertility represents a major gap in our knowledge of reproductive biology. Most significantly, an integrated understanding of ovarian processes needs be addressed using global analyses. Nuclear receptors, (e.g. the estrogen receptor), regulate cell functions in the ovary and in other tissues. The molecules that trigger the action of some other nuclear receptors are unknown. These are the orphan nuclear receptors. We propose to continue study of two orphan receptors, known as Sf-1 and Lrh-1, that we have shown to be essential for ovarian development and ovulation. Our study will employ transgenic mouse models where these receptors have been depleted, and human granulosa cells derived from in vitro fertilization clinics. Global approaches will lead to the discovery of the role of orphan nuclear receptors in infertility.