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Ddx4+ Oogonial Stem Cells in Postmenopausal Women's Ovaries: A Controversial, Undefined Role
Erica Silvestris1,2, Paola Cafforio3, Claudia Felici4
1Gynecologic Oncology Unit, I.R.C.C.S-Giovanni Paolo II Cancer Institute, 70124 Bari, Italy. ericasilvestris85@gmail.com.
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.
Insights
Oogonial stem cells (OSCs) exist in women
Area of Science:
- Reproductive Biology
- Stem Cell Research
- Gynecology
Background:
- Recent studies suggest the presence of oogonial stem cells (OSCs) in the mammalian ovarian cortex, including humans.
- These cells exhibit stemness properties and can differentiate into oocyte-like cells in vitro.
- The existence of OSCs challenges the traditional view of a finite oocyte pool that depletes with menopause.
Purpose of the Study:
- To explore the presence and characteristics of oogonial stem cells (OSCs) in the ovarian cortex of women.
- To investigate the potential role of OSCs in female fertility, ovarian aging, and carcinogenesis.
- To highlight the therapeutic potential of OSCs for restoring ovarian reserve.
Main Methods:
- Characterization of OSCs based on size and membrane expression of DEAD(Asp-Glu-Ala-Asp)-box polypeptide-4 (Ddx4).
- Assessment of stemness properties including self-renewal and clonal expansion.
- In vitro differentiation assays to evaluate the potential of OSCs to form oocyte-like cells.
- Detection of OSCs in postmenopausal women and ovarian tumor samples.
Main Results:
- OSCs are found in the ovarian cortex of women, exhibiting stemness and differentiation capabilities.
- Viable OSCs capable of differentiating into oocytes are present even in postmenopausal women.
- Ddx4+ cells, potentially OSCs, are observed in ovarian tumors, suggesting a role in carcinogenesis.
- OSCs can differentiate into somatic cells under specific stimuli.
Conclusions:
- The discovery of OSCs necessitates a re-evaluation of the established theory of oocyte pool exhaustion.
- OSCs may play a role in ovarian aging and potentially in ovarian cancer development.
- OSCs represent a promising avenue for therapeutic interventions aimed at restoring ovarian function and fertility in various clinical scenarios.
- Further research is crucial to fully elucidate the function of OSCs in ovarian physiology and pathology.