Ovarian germline stem cells: an unlimited source of oocytes?

While there has been progress in directing the development of embryonic stem cells and induced pluripotent stem cells toward a germ cell state, their ability to serve as a source of functional oocytes in a clinically relevant model or situation has yet to be established. Recent studies suggest that the adult mammalian ovary is not endowed with a finite number of oocytes, but instead possesses stem cells that contribute to their renewal. The ability to isolate and promote the growth and development of such ovarian germline stem cells (GSCs) would provide a novel means to treat infertility in women. Although such ovarian GSCs are well characterized in nonmammalian model organisms, the findings that support the existence of adult ovarian GSCs in mammals have been met with considerable evidence that disputes their existence. This review details the lessons provided by model organisms that successfully utilize ovarian GSCs to allow for a continual and high level of female germ cell production throughout their life, with a specific focus on the cellular mechanisms involved in GSC self-renewal and oocyte development. Such an overview of the role that oogonial stem cells play in maintaining fertility in nonmammalian species serves as a backdrop for the data generated to date that supports or disputes the existence of GSCs in mammals as well as the future of this area of research in terms of its potential for any application in reproductive medicine.