Infertility affects 6.1 million individuals and their partners in the United States. The underlying causes of many cases of infertility are not known. The germ cell lineage is central to fertility, as this cell lineage is ultimately responsible for creating eggs and sperm. Therefore, abnormal formation and function of germ cells would undoubtedly be a major cause of infertility. Formation of human germ cells begins very early in fetal life. During this time, fetal germ line cells undergo germ cell-specific reprogramming events to create the foundation upon which further germ cell differentiation into functional gametes can occur. Currently, we do not understand the basic mechanisms by which human fetal germ cells differentiate, or undergo germ cell reprogramming. This lack of understanding is due to the fact that up until recently, there has been no robust method for examining human germ cell formation during fetal life. Now, the use of human pluripotent stem cells has created the opportunity to generate fetal germ cells in the lab, and to use these in vitro derived germ cells to study the basic mechanisms that control germ cell differentiation. Using this method the experiments outlined in this proposal are directed at understanding how the supporting cells of the fetal gonad regulate differentiation of human fetal germ cells. Results from this work are directed towards establishing the enabling technology for understanding the basic mechanisms that regulate germ cell formation and therefore deciphering the underlying causes of human infertility, germ cell tumors or birth defects.
In the short term, the proposed research is designed to create jobs as a technical position will be created to undertake the proposed research program. In the long term, the goal of the proposed research is to create new technology which could be used by academic, research and development or pharmaceutical laboratories. Finally, this research program is ultimately designed to benefit human reproductive health. This problem is not restricted to Californians, however 6.1 million individuals and their partners are diagnosed as infertile in the United States, and results from this grant are designed to understand the underlying causes of this disease.