Ovarian germline stem cells: an unlimited source of oocytes?

Abstract

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.

Keywords: Ovarian germline stem cells; fertility; oocytes.

Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

The spatial arrangement of the GSC niche in Drosophila. The stem cell niche is comprised of the somatic cells that include those in the terminal filament and cap cells, which provide signals necessary for GSC self-renewal.

Figure 2

The spatial arrangement of the GSC niche in C. elegans. Mitotic GSCs are in close proximity to the distal cap cell, the somatic cell responsible for maintaining adjacent cells in an undifferentiated state. Once GSCs are several cell layers removed from the distal cap cells, they differentiate and undergo meiosis

Figure 3

The spatial arrangement of the GSC niche in medaka. GSCs reside in the germinal epithelium, a region that lies in between the basement membrane and the epithelial cells. GSC maintenance and renewal is regulated by adjacent SOX9b expressing somatic cells.