Disorganization of the germ cell pool leads to primary ovarian insufficiency.

The mammalian ovary is an organ that controls female germ cell development, storing them and releasing mature oocytes for transporting to the oviduct. During the fetal stage, female germ cells change from a proliferative state to meiosis before forming follicles with the potential for the growth of surrounding somatic cells. Understanding of molecular and physiological bases of germ cell development in the fetal ovary contributed not only to the elucidation of genetic disorders in primary ovarian insufficiency (POI), but also to the advancement of novel treatments for patients with POI. Accumulating evidence indicates that mutations in NOBOX, DAZL and FIGLAgenes are associated with POI. In addition, cell biology studies revealed the important roles of these genes as essential translational factors for germ cell development. Recent insights into the role of the PI3K (phosphatidylinositol 3-kinase)-Akt signaling pathway in primordial follicle activation allowed the development of a new infertility treatment, IVA (in vitro activation), leading to successful pregnancy/delivery in POI patients. Furthermore, elucidation of genetic dynamics underlying female germ cell development could allow regeneration of oocytes from ES (embryonic stem)/iPS (induced pluripotent stem) cells in mammals. The purpose of this review is to summarize basic findings related to female germ cell development and potential clinical implications, especially focusing on POI etiologies. We also summarize evolving new POI therapies based on IVA as well as oocyte regeneration.