Ovarian germline stem cells

Cheryl E Dunlop, Evelyn E Telfer, Richard A Anderson

It has long been established that germline stem cells (GSCs) are responsible for lifelong gametogenesis in males, and some female invertebrates (for example, Drosophila) and lower vertebrates (for example, teleost fish and some prosimians) also appear to rely on GSCs to replenish their oocyte reserve in adulthood. However, the presence of such cells in the majority of female mammals is controversial, and the idea of a fixed ovarian reserve determined at birth is the prevailing belief among reproductive biologists. However, accumulating evidence demonstrates the isolation and culture of putative GSCs from the ovaries of adult mice and humans. Live offspring have been reportedly produced from the culture of adult mouse GSCs, and human GSCs formed primordial follicles using a mouse xenograft model. If GSCs were present in adult female ovaries, it could be postulated that the occurrence of menopause is not due to the exhaustion of a fixed supply of oocytes but instead is a result of GSC and somatic cell aging. Alternatively, they may be benign under normal physiological conditions. If their existence were confirmed, female GSCs could have many potential applications in both basic science and clinical therapies. GSCs not only may provide a valuable model for germ cell development and maturation but may have a role in the field of fertility preservation, with women potentially being able to store GSCs or GSC-derived oocytes from their own ovaries prior to infertility-inducing treatments. Essential future work in this field will include further independent corroboration of the existence of GSCs in female mammals and the demonstration of the production of mature competent oocytes from GSCs cultured entirely in vitro.