Experimental evidence showing that no mitotically active female germline progenitors exist in postnatal mouse ovaries

Abstract

It has been generally accepted for more than half a century that, in most mammalian species, oocytes cannot renew themselves in postnatal or adult life, and that the number of oocytes is already fixed in fetal or neonatal ovaries. This assumption, however, has been challenged over the past decade. In this study, we have taken an endogenous genetic approach to this question and generated a multiple fluorescent Rosa26 rbw/+ ;Ddx4-Cre germline reporter mouse model for in vivo and in vitro tracing of the development of female germline cell lineage. Through live cell imaging and de novo folliculogenesis experiments, we show that the Ddx4-expressing cells from postnatal mouse ovaries did not enter mitosis, nor did they contribute to oocytes during de novo folliculogenesis. Our results provide evidence that supports the traditional view that no postnatal follicular renewal occurs in mammals, and no mitotically active Ddx4-expressing female germline progenitors exist in postnatal mouse ovaries.

Life-long in vivo cell-lineage tracing shows that no oogenesis originates from putative germline stem cells in adult mice

“…For example, by tracing the proliferation of cultured Ddx4-positive cells in vitro, a recent study from our group reported that no mitotically active GSCs exist in the postnatal mouse ovary (10). More recently, Lei and Spradling provided evidence to support our findings by showing that no active GSCs could be detected in adult mouse ovaries (11).…”

“…In contrast to these reports, other recent reports have provided evidence that adult oogenesis and the so-called GSCs do not exist and have questioned the above-mentioned findings (8)(9)(10)(11)(12). For example, by tracing the proliferation of cultured Ddx4-positive cells in vitro, a recent study from our group reported that no mitotically active GSCs exist in the postnatal mouse ovary (10).…”

Seeking the origin of female germline stem cells in the mammalian ovary

“…Finally, a purified population of PGCs could be injected into ovaries to investigate whether de novo folliculogenesis occurs. This last experimental approach has been recently used by Zhang et al (2012) and by us and will be discussed in the next section.…”

“…Thus, retention in small cysts might represent the way to preserve undifferentiated PGCs within the post-natal ovary. Some evidence exists that in the mouse and in some primate species, including humans pre-meiotic proliferating PGCs/oogonia remain in the post-natal ovary during the first period after birth perhaps until puberty (Motta & Makabe 1982, McClellan et al 2003, Johnson et al 2004, Telfer 2004, Byskov et al 2011, Zhang et al 2012. The question of whether any of these proliferating germ cells become follicle-enclosed oocytes remains open.…”

“…In an effort to ascertain the existence of FGSCs in post-natal mouse ovaries, it has recently been shown Origin of female germline stem cells R127 that adult mouse ovaries are able to support the formation of new follicles when provided with premeiotic female PGCs and companion pre-follicular cells; transplanted PGCs were, however, able to form follicles only with their own pre-follicular cells and these latter only with the transplanted PGCs (Zhang et al 2012). Although from these and other results, the authors concluded that 'neo-oogenesis' does not occur in adult mouse ovaries; nevertheless, these results give a positive answer to the important question as to whether the adult ovary is able to support 'neooogenesis' from PGCs.…”