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 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. While such ovarian GSCs are well-characterized in non-mammalian model organisms, the findings that support the existence of adult ovarian GSCs in mammals have been met with considerable evidence that disputes their existence. Thus, 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 oogonial stem cells play in maintaining fertility in non-mammalian 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.

Epigenetic inheritance through the female germ-line: The known, the unknown, and the possible

“…The ovaries of a newborn female mouse harbor about 8000 primordial follicles [9], and those of a newborn girl about 1,000,000 [10]. There is some debate whether a population of ovarian germ-line stem cells exists postnatally, but the weight of available evidence indicates that no new oocytes are generated in mammals after birth [11][12][13][14].…”

Germline Development of Genetically Female Nile Tilapia (<b><i>Oreochromis niloticus</i></b>) Reared under Different Temperature Regimes

“…In contrast to female mammals which have only a finite number of germ cells, teleost germ cells exhibit a lifelong ability to multiply [Hanna and Hennebold, 2014]. On the male side, teleosts show similar characteristics as mammals, featuring germline stem cells.…”

“…A unique characteristic of the female teleost germline is the capability of proliferating throughout the entire lifespan [Wildner et al, 2013;Hanna and Hennebold, 2014]. Grier et al [2007] stated that the germinal epithelium is a source of germline stem cells both in male and female individuals.…”

Genetics of Gonadal Stem Cell Renewal

“…GSCs are therefore undetectable in adult mouse ovaries, and single-cell lineage tracing has shown unequivocally that the pool of primordial follicles is maintained without input from GSCs (Zhang et al 2012, Lei & Spradling 2013, Hanna & Hennebold 2014). By contrast, the Drosophila ovary contains GSCs that remain active and support continuous egg production throughout adulthood.…”