Abstract
Recent studies support the existence of oogonial stem cells (OSCs) in the ovarian cortex of different mammals, including women.These cells are characterized by small size, membrane expression of DEAD(Asp-Glu-Ala-Asp)-box polypeptide-4 (Ddx4), and stemness properties (such as self-renewal and clonal expansion) as well as the ability to differentiate in vitro into oocyte-like cells. However, the discovery of OSCs contrasts with the popular theory that there is a numerically defined oocyte pool for female fertility which undergoes exhaustion with menopause. Indeed, in the ovarian cortex of postmenopausal women OSCs have been detected that possess both viability and capability to differentiate into oocytes, which is similar to those observed in younger patients. The pathophysiological role of this cell population in aged women is still debated since OSCs, under appropriate stimuli, differentiate into somatic cells, and the occurrence of Ddx4+ cells in ovarian tumor samples also suggests their potential involvement in carcinogenesis. Although further investigation into these observations is needed to clarify OSC function in ovary physiology, clinical investigators and researchers studying female infertility are presently focusing on OSCs as a novel opportunity to restore ovarian reserve in both young women undergoing early ovarian failure and cancer survivors experiencing iatrogenic menopause.
Highlights
Important to oogonial stem cells (OSCs) detection and isolation was the proof that OSCs express the DEAD (Asp-Glu-Ala-Asp)-box polypeptide-4 (Ddx4) molecule, a primordial oogonial marker encoded by the relative gene as an ATP-dependent RNA helicase belonging to the DEAD-box protein family
We have recently explored this aspect in Ddx4+ OSCs and found interesting information concerning the putative fate of these cells in ovaries during the postmenopausal stage of women
Recent advances in the field of regenerative medicine have focused on the application of OSCs, which, because of their ability to differentiate into oocyte-like cells in vitro, are considered a promising therapeutic approach to infertility and menopause
Summary
The theoretical physiology of mammalian fertility has long supported the belief that a fixed pool of oocytes, including approximately 100 progenitors during the time of puberty in women, is committed to providing the mature oocytes that span the duration of female fertility, and that this ovarian reserve undergoes a progressive decrease with aging until complete exhaustion occurs at menopause [1].Along with the recent evolution of major studies in the field of stemness and regenerative medicine, basic science and clinical researchers investigated the supposed existence of oogonial stem cells (OSCs) that, for their staminal properties (including self-renewal, clonal expansion, and predictable differentiation into oocyte-like cells), would offer an interesting application in redressing ovarian failure in infertile women [2].Observations of OSCs by independent groups of investigators provided evidence of the existence of OSCs within the murine ovarian cortex [3,4,5]. And co-workers [10] purified mitotically active OSCs from the ovarian cortex of fertile women by sorting Ddx4+ cells that appeared very small (4 μm diameter) and expressed primordial germline markers.
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