Female mice lack adult germ-line stem cells but sustain oogenesis using stable primordial follicles

Abstract

Whether or not mammalian females generate new oocytes during adulthood from germ-line stem cells to sustain the ovarian follicle pool has recently generated controversy. We used a sensitive lineagelabeling system to determine whether stem cells are needed in female adult mice to compensate for follicular losses and to directly identify active germ-line stem cells. Primordial follicles generated during fetal life are highly stable, with a half-life during adulthood of 10 mo, and thus are sufficient to sustain adult oogenesis without a source of renewal. Moreover, in normal mice or following germ-cell depletion with Busulfan, only stable, single oocytes are lineage-labeled, rather than cell clusters indicative of new oocyte formation. Even one germline stem cell division per 2 wk would have been detected by our method, based on the kinetics of fetal follicle formation. Thus, adult female mice neither require nor contain active germ-line stem cells or produce new oocytes in vivo.

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).…”

Ovarian stem cells: From basic to clinical applications

“…Long-term expanded mouse ovarian GSCs maintain their characteristics, telomerase activity and express germ cell and stem cell markers White et al [7] The ovarian GSCs are isolated by FACS. Xenotransplantation of human GCSs into NOD-SCID mice leads to the formation of follicles containing oocytes Zhang et al [32] No mitotically active female GSCs exist in postnatal mouse ovaries Lei et al [33] The adult female mouse ovary does not contain active ovarian GSCs. The number of follicles produced during fetal development is sufficient to provide ovaries with oocytes in adult life Park et al [39] Existence of mitotically active germ cells in the postnatal mouse ovary demonstrated by a genetic approach coupled with a GSCs selection strategy chemotherapy followed by BM or PB transplantation.…”

“…After the publication of the above-mentioned studies, two different groups presented contradictory results [32,33] . These investigators refuted the existence of GSCs in the adult ovary and provided evidence supporting the dogma of a fixed pool of oocytes after birth.…”

Increased DNA damage and repair deficiency in granulosa cells are associated with ovarian aging in rhesus monkey

“…By age 50 ovarian reserve is nearly completely exhausted [3]. Unlike males having germline stem cells and germ cell renewal, females do not contain germline stem cells and do not undergo germ cell renewal [4][5][6][7], resulting in a limited reproductive lifespan. Women undergo follicle depletion and experience menopause by the age of approximately 50.…”