The adult mammalian ovary has been under surveillance for over 10 years now since it was proposed to harbor stem cells that experience postnatal oogenesis during the reproductive period such as spermatogenesis in the testes. Ovarian stem cells are found in the surface epithelium of the adult and menopausal ovary and also in the ovary with early failure. Ovarian stem cells contain two particular populations, including very small, round embryonic stem cells (VSELs expressing nuclear OCT-4 and other particular markers of pluripotent and primordial germ cells) and slightly larger ovarian germ stem cells (OGSCs with OCT-4 cytoplasmic which are identical to the spermatogonial stem cells of the testicles). These stem cells can unexpectedly differentiate into egg-like structures in vitro. Stem cells can also be derived from bone marrow and therefore can serve as an alternative source. Ovarian stem cells express FSHR and respond to FSH by experiencing self-renewal, clonal extension, and the initiation of neo-oogenesis and primordial follicle assembly. VSELs are largely silent and have been reported to survive chemotherapy and initiate oogenesis in mice when exposed to FSH. This growing understanding and further research in the field will help advance new methodologies to monitor ovarian pathologies and, furthermore, towards oncofertility. Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get an original essay IntroductionThe idea that a woman is born with a fixed pool of follicles was addressed by Professor Tilly in 2004 and his colleagues who revived the essential concept of postnatal oogenesis and showed us that the rate of Oocyte loss in mouse ovaries due to atresia and ovulation was in fact restored by a continuous supply of immature oocytes that maintains a steady state [2]. These perceptions supported the idea of ​​immature ovarian stem cells and postnatal oogenesis, and some minds were drawn to this area of ​​research. The first significant advance was to demonstrate the presence of stem cells in the ovary, followed by how they function under normal conditions by stimulating postnatal oogenesis. and how they cause various pathologies such as ovarian failure, menopause and cancer. Likewise, it has become important to examine whether undeveloped cells present in the ovary of adult mammals could be controlled to regain ovarian capacity under certain particular conditions, for example after oncotherapy in tumor survivors. Previously, postnatal follicular regeneration in the mouse ovary [3] and ovarian surface epithelium (OSE) was considered as a source of germ cells in the ovary at the fetal stage [4, 5]. It has therefore been suggested that the OSE is the dynamic starting point of malignancies and that approximately 90% of ovarian cancers emerge from the OSE [6]. Several techniques such as label-retaining cells, Hoechst dye blocking side population have established stem cells [7-9], and a new stem cell population co-expressing Lin28 and Oct-4 in ovarian epithelial growths have been established [10]. Flesken-Nikitin et al. [11] verified the presence of stem cells in the OSE in the hilus area as a niche for ovarian cancer cells. The present article provides a brief review of our current knowledge on ovarian stem cells, their origin and characteristics, and how they are involved in postnatal oogenesis along with the remarkable developmental expressing receptorsfollicle-stimulating hormone (FSHR) and are modulated by FSH to occur. -renewal, clonal extension to form germ cell nests, proliferation, differentiation and assembly of the primordial follicle (PF) in the adult ovary. The adult mammalian ovary hosts stem cells, progenitors, and germ cell nests. The adult mammalian ovary is responsible for providing mature, competent oocytes for reproduction. Furthermore, it is responsible for the secretion of various hormones, growth factors and cytokines involved in the signaling pathways of folliculogenesis and oogenesis. It is a vibrant organ lined by a solitary layer of cuboidal-surfaced germinal epithelial cells that is generally less dedifferentiated and uncommitted and under typical conditions expresses epithelial and mesenchymal markers. The OSE plays a role in ovulation, the arrival of the mature oocyte, the subsequent ovarian remodeling and the repair of follicular dividers and then turns into a spasmodic layer in case of anovulatory cycles, anovulatory cycles, polycystic ovary disorder and during menopause and in sclerotic ovaries [6]. The first confirmation of the presence of ovarian stem cells in OSE was given by Tilly's group [2] when they demonstrated cells coexpressing MVH and BrdU in OSE together with meiotic markers (Scp3, Spo11, and Dmc1) and that on the union of the wild-type ovary in the OSE GFP mice stimulated the development of follicles with GFP oocytes enclosed by wild-type granulosa cells. Since then, several research groups have been committed to involving and examining ovarian stem cells with the assistance of different methodologies such as immunomagnetic antibodies and cell organization procedures based on flow cytometry (MACS and FACS), in vitro culture and cell differentiation. ovarian stem cells, genetic linkage tracing and transplantation assays, suggesting that the follicular pool is certainly not a static pool but definitely a dynamic population of differentiation and regression of structure in adult mice and human ovaries. A detailed report on stem cells in adult mammalian ovaries was first provided by Tilly and Bukovsky's groups. Both groups found a favorable influence of bone marrow cells on ovarian function. While Bukovsky's team found that OSE cells give rise to structures somewhat similar to oocytes in vitro, at the same time Tilly and Virant-Klun's groups reported the presence of stem cells in POF and menopausal women. Tilly's team successfully validated the PF niche in ovarian cortical tissue samples in vitro using specific markers of PGCs, germ cells and primordial oocytes. [21]. The Virant-Klun group reported the presence of very small, 4 ????m spherical cells expressing pluripotent and PGC-specific markers [23]. Johnson et al. [18] reported the presence of specific transcripts of PGCs (Stella, Fragilis and Nobox) and germ cells (Oct4, Mvh and Dazl) in the bone marrow. Bhartiya's team, with the help of Bukovsky, reported the presence of stem cells in the OSE of sheep, monkey, rabbit and humans and for the first time demonstrated that the OSE harbors two distinct types of stem cells, including including (i) spherical cells that were smaller than red blood cells in agreement with Virant-Klun observations and (ii) a slightly larger “progenitor” population. Immunolocalization studies demonstrated that the smaller cells were pluripotent and expressed nuclear OCT-4, whereas the larger cells expressed cytoplasmic OCT-4. An extensive review of the literature revealed that Professor Ratajczak's group had encountered similar cells called embryonic stem cellsvery small (VSEL) in various adult tissues [24]. VSELs are the smallest cells with OCT-4 nuclear markers, and the cells with cytoplasmic OCT-4 were germinal stem cells (OGSCs) and resemble the oogonial stem cells (OSCs) described by Tilly's group. The comprehensive procedures to study these cells (VSEL, OGSC and GCN) by mechanical curettage of larger mammalian ovaries and after enzymatic digestion of mouse OSE were recently described by us [12]. The presence of germ cell markers in the bone marrow and the expression of PGC markers on these stem cells suggests the presence of a common population of VSELs in the bone marrow/peripheral blood and ovaries, as suggested by Ratajczak's group [25]. The presence of stem cells and GCN in the adult ovary contradicts the report of Lei and Spradling [26], and the technical reasons leading to the discrepancy have been discussed [22]. The existence of stem cells in mammalian ovaries has not yet been widely recognized; rather, there are groups that have produced evidence against the presence of stem cells in the ovary of adult mammals. This obviously suggests that further field research is needed. The above investigation demonstrates that key microorganisms exist in the OSE and we currently end up seeing how these stem cells function and add to postnatal oogenesis in ordinary adult mammalian ovaries. Presence of FSHR and FSH Action on Ovarian Stem Cells Current belief in reproductive biology suggests that in the ovary only granulosa cells harbor FSHR and initial follicle growth is gonadotropin independent. Various scientists have already published reports on various concepts regarding the existence and action of FSHR in ovarian stem cells. Sairam's group reported that alternative splicing of sheep ovarian and testicular FSHR produces 4 distinct isoforms of which FSHR1 and FSHR3 have biological roles [28]. Babu et al. [29] stated that when the mouse ovary is exposed to PMSG treatment, FSHR isoforms with varied expression are formed. Both FSHR1 and FSHR3 isoforms were detected by RT-PCR in normal ovary, and FSHR3 expression was found to be selectively increased after 24 and 48 hours of PMSG treatment. Western blotting confirmed the presence and upregulation of FSHR3 in the ovary after PMSG treatment using an FSHR3-specific IgG peptide. Sullivan et al. [30] studied the relative mRNA expression for alternatively spliced ​​FSHR transcripts (FSHR1, FSHR2 and FSHR3) and LHR [14]. These findings are especially significant in light of how no critical affiliation was observed between transformations or single nucleotide polymorphisms (SNPs) in the undoubted FSHR1 with premature ovarian failure and infertility. The Bartiya group in their review discussed the probable role of FSHFSHR3 stem cell binding in OSE causing ovarian tumors, POF and menopause and how scientists were fooled by screening for changes in FSHR1 with an emphasis on the exon 10 through FSHR3 might have a more important role (has exon 11 and requires exons 9 and 10) thus clarifying the accumulated negative information about the absence of transformations in FSHR in women with POF and cancer [31]. The results of this team propose a unique approach to the activity of FSH on stem cells located in the OSE and call for a change of perspectives in the field of reproductive biology. A recent study describes the presence of gonadotropin receptors on human bone marrow hematopoietic progenitors, including VSELs [32], supporting a developmental link between hematopoiesis and the germline. Turns outIt is quite disconcerting how FSH affects the ovaries when an infertility expert treats a woman in the clinic for egg retrieval or assisted reproduction. Does FSH really only play a survival role on ovarian follicles, preventing cell death of a cohort of oocytes as they begin to develop, or does FSH treatment apply coordinated activity on ovarian stem cells preventing cell death of a cohort of oocytes when they start to grow or is it perhaps because the FSH treatment exerts a direct action on the ovarian stem cells and a completely new cohort of follicles assembles and starts to grow from the stem cells! We need better means to interpret these well-kept mysteries of Mother Nature on the surface of the ovary. In humans, the process of initiation of follicle maturation from the primordial pool is totally independent of gonadotropins. Although FSH is a major factor regulating folliculogenesis, the “initial recruitment” of human PF is mostly controlled by factors synthesized in the ovaries [1]. In general FSH is secreted at high levels at mid-cycle (preovulatory peak), but there is another smaller peak that occurs during the late luteal phase and is called the “intercycle peak” in humans or the “proestrus peak” (secondary peak) in rodents and is thought to be associated with the recruitment of follicles for the next cycle. Rani and Moudgal [60] demonstrated that instead of the “preovulatory” FSH peak, the “proestrus” peak influences follicular growth and blocks ovulation in the following cycle. It is likely this intercycling surge in FSH that triggers stem cell activity in the OSE, resulting in PF assembly [15] and these follicles then rapidly grow and mature. But more carefully planned studies need to be undertaken to generate more evidence to support this preliminary observation. Germ stem cell niche in adult ovaries A characteristic property of stem cell activity found in adult mammalian ovaries is the location of cyst germ cell nests in them [26]. In recent years, Zhang et al. [27] using 3 genetically modified adult mouse models provided strong evidence criticizing stem cell activity and postnatal oogenesis. Their research suggests that there is no production of oocytes from stem cells in the adult ovary and that somatic cells are not recruited to help assembly of the primordial follicle with de novo regenerated oocytes. Unlike their experiment where genetic manipulations are performed to answer a biological question, Bhartiya's team used a more technical approach to give convincing answers to the same question about postnatal oogenesis [16]. They first characterized stem cells in enzymatically separated OSE cells and used flow cytometry to study LIN−/CD45−/SCA+ VSELs in normal adult ovaries (0.02 + 0.01%) and chemoablated mouse ovaries (0 .03 + 0.017%). VSELs survive chemotherapy and 48 hours of PMSG treatment on the chemoablated ovary resulted in an increase in their number (0.08 + 0.03%) accompanied by the onset of neo-oogenesis in the OSE layer. The process was modulated by FSH in both culture of mechanically isolated OSE cells and culture of intact adult chemoablated ovary. Successful formation of germ cell nests was observed and the manuscript was accepted for publication after a very rigorous review process. Oocytes can be obtained from endogenous VSEL/OSCs or iPS cells. Horan and Williams [36] in their review suggested the probable use of induced pluripotent stem (iPS) cells in..