Cell-cell interactions in primordial ovarian follicle assembly and development

The assembly of the developmentally arrested primordial ovarian follicle and that structures subsequent transition to the growing primary follicle are poorly understood processes critical for female reproduction. The primordial follicles do not proliferate and when the make the transition to the primary follicle they will be destroyed at ovulation or oocyte atresia. The primordial follicles represent the sole source of oocytes and ovarian steroidogeneic cells. When the primordial follicles in humans are depleted the physiological condition of menopause begins. Dysfunction in primordial follicle assembly and the primordial to primary follicle transition cause a premature loss of primordial follicles, which leads to pathological conditions such as premature ovarian failure. This dissertation describes many novel regulatory mechanisms for primordial follicle assembly and the primordial to primary follicle transition. A combination of rat organ culture and in vivo studies developed a model of steroid control of primordial follicle assembly. Specifically maternal progesterone retarded primordial follicle assembly until birth removed the female rat from the high steroid concentration. This is the first control mechanism for primordial follicle assembly postulated. The results of organ culture experiments determined that insulin promoted the primordial to primary follicle transition. The important regulator of large antral follicle development IGF-1 did not promote the primordial to primary follicle transition. Results of organ culture experiments determined that the usually mesenchymal growth factor keratinocyte growth factor promoted the primordial to primary follicle transition. This suggests the importance of epithelial mesenchymal cell-cell interactions in primordial follicle biology. RNA from unassembled, primordial, and primary follicles was analyzed on a 6000-gene rat microarray gene chip. Many possible regulatory mechanisms were identified. These include the role of neu differentiation factors in primordial follicle assembly and Platelet Derived Growth Factor in the primordial to primary follicle transition. In summary several significant contributions to the knowledge of primordial follicle assembly and the primordial to primary follicle transition have been made. By studying the coordination of these processes understanding and possible treatments of pathological conditions such as premature ovarian failure will be made.