The adult mammalian ovary has been under scrutiny for over 10 years now, ever since it was proposed to harbor stem cells that undergo postnatal oogenesis during the reproductive period, such as spermatogenesis in the testes. Ovarian stem cells are located in the surface epithelium of the adult and menopausal ovary as well as in the ovary with early failure. Ovarian stem cells contain two special populations: very small, round embryonic cells (VSELs which express nuclear OCT-4 and other specific markers of pluripotent and primordial germ cells) and somewhat larger ovarian germ cells ( OGSCs with cytoplasmic OCT-4 which are identical to spermatogonial stem cells of the testis). These stem cells can unexpectedly differentiate into oocyte-like structures in vitro. Stem cells can also come from bone marrow and can therefore serve as an alternative source. Ovarian stem cells express FSHR and respond to FSH by undergoing self-renewal, clonal expansion, and initiating neo-oogenesis and assembly of primordial follicles. VSELs are largely silent and have been reported to survive chemotherapy and trigger oogenesis in mice when exposed to FSH. This growing understanding and continued research in the field will help advance new methodologies to monitor ovarian pathologies and, furthermore, oncofertility. Say no to plagiarism. Get a tailor-made essay on “Why violent video games should not be banned”?Get the original essayIntroductionThe idea that a woman is born with a fixed pool of follicles was confronted by Professor Tilly in 2004 and his colleagues who have revived the essential nature of the ban on violent video games. theme of postnatal oogenesis and proved to us that the rate of oocyte loss in mouse ovaries due to atresia and ovulation was in fact replenished by a continuous supply of immature oocytes which maintain a state balance [2]. These perceptions supported the idea of ​​ovarian immature 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 their functioning under ordinary conditions, causing postnatal oogenesis. , and how they lead to different pathologies such as ovarian disappointment, menopause and cancer. Likewise, it appeared relevant to examine whether undeveloped cells present in the ovary of an adult mammal could be controlled to recover ovarian capacity under certain specific conditions, for example after oncotherapy in survivors of a tumor. Postnatal follicular regeneration in the mouse ovary [3] and ovarian surface epithelium (OSE) as a source of germ cells in the mid-ovary at the fetal stage has been considered in the past [4, 5]. It has therefore been suggested that the OSE is the dynamic starting site of neoplasms and that approximately 90% of ovarian tumors emerge from the OSE [6]. Different techniques such as cell retaining labels, side population excluding Hoechst dye confirmed stem cells [7–9] and a novel population of stem-like cells coexpressing Lin28 and Oct-4 in ovarian epithelial growths have been described [10]. Flesken-Nikitin et al. [11] verified the presence of stem cells in the OSE at the hilum as a niche for the cellsovarian cancers. The present article provides a brief overview of our current knowledge of ovarian stem cells, their source and characteristics, and how they are involved in postnatal oogenesis, alongside a remarkable development that they express follicle hormone receptors. -stimulating (FSHR) and are modulated by FSH to self-expose. -renewal, clonal expansion to form germ cell nests, proliferation, differentiation and assembly of the primordial follicle (PF) in the adult ovary. The ovary of adult mammals houses stem cells, progenitors, and germ cell nests. The ovary of adult mammals is responsible for providing mature, reproductively competent oocytes. In addition, it is responsible for the secretion of various hormones, growth factors and cytokines involved in the folliculogenesis and oogenesis signaling pathways. It is a vibrating organ lined by a solitary layer of germinal epithelial cells with a cuboidal surface that is generally less dedifferentiated and unengaged 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 the follicular dividers and thus transforms into a spasmodic layer in the event of anovulatory cycles, disorders of the polycystic ovaries and in 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 the OSE alongside meiotic markers (Scp3, Spo11 and Dmc1) and that of wild-type ovary union in GFP mice caused the development of follicles with GFP oocytes surrounded by wild-type granulosa cells . From then on, different research groups have embarked on the involvement and examination of ovarian stem cells using various methodologies such as immunomagnetic antibody-based cell arrangement procedures and flow cytometry. (MACS and FACS), in vitro culture and differentiation of ovarian stem cells, genetic linkage tracing. and transplantation assays, proposing that the pool of follicles is certainly not a static population, but indeed a dynamic population of differentiating and regressing structure in adult mice and human ovaries. A detailed report on stem cells in adult mammalian ovaries was first presented by Tilly's and Bukovsky's groups. Both groups noted 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, Tilly and Virant-Klun's groups reported the presence of stem cells in POF and postmenopausal women. Tilly's team successfully validated the PF niche in the ovarian cortex. tissue samples in vitro using PGCs, germ cells and primordial oocyte specific markers. [21].The Virant-Klun group reported the presence of very small spherical cells of 4 ????m which express pluripotent and specific markers of PGCs [23]. Johnson et al. [18] reported the presence of PGC (Stella, Fragilis and Nobox) and germ cell (Oct4, Mvh and Dazl) specific transcripts in bone marrow. Bhartiya's team, with help from Bukovsky, reported the presence of stem cells in sheep, monkey, rabbit and human OSE and demonstrated for the first time that OSE harbors two distinct typesstem cells, including (i) spherical cells that were smaller than red blood cells, consistent with Virant-Klun's observations and (ii) a slightly larger population of “progenitors”. Immunolocalization studies showed that smaller cells were pluripotent and expressed nuclear OCT-4, while larger cells expressed cytoplasmic OCT-4. A thorough review of the literature revealed that Professor Ratajczak's group had reported similar cells called very small embryonic-like stem (VSEL) cells in various adult tissues [24]. VSELs are the smaller cells with nuclear OCT-4 markers and the cells with cytoplasmic OCT-4 were the germline stem cells (OGSCs) and resemble the oogonial stem cells (OSCs) described by Tilly's group. Extensive procedures to study these cells (VSEL, OGSC and GCN) by mechanical scraping 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 suggest the presence of a common population of VSELs in the bone marrow/peripheral blood and ovaries, as suggested by the group of Ratajczák [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 this discrepancy have been discussed [22]. The existence of stem cells in the mammalian ovary is not yet widely recognized; Rather, there are groups that have produced evidence against the presence of stem cells in the ovary of an adult mammal. This obviously suggests that further research is needed in this area. The study of the above writings demonstrates that fundamental microorganisms exist in the OSE and it currently ends up seeing how these stem cells function and add to postnatal oogenesis in the ovaries of ordinary adult mammals. Presence of FSHR and action of FSH on ovarian stem cells Current belief in reproductive biology suggests that in the ovary, only granulosa cells harbor FSHR and that initial follicle growth is independent of gonadotropins . 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 are formed with varied expression. Both isoforms FSHR1 and FSHR3 were detected by RT-PCR in normal ovary and it was found that FSHR3 expression was selectively increased after 24 and 48 h 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] investigated the relative mRNA expression for alternatively spliced ​​FSHR transcripts (FSHR1, FSHR2 and FSHR3) and LHR [14]. These results are particularly important in light of the fact that no critical affiliations were observed between transformations or single nucleotide polymorphisms. (SNP) in unquestionable FSHR1 with premature ovarian failure and infertility. The Bartiya group, in its review, deliberated on the probable role of FSHFSHR3 stem cell association in OSE causing ovarian cancers, POF and menopause and how scientists havebeen misled by screening for changes in FSHR1 with a focus on exon 10 via FSHR3. may have a more important role (has exon 11 and needs exons 9 and 10) thus clarifying the negative information accumulated about the absence of transformations in FSHR in women with POF and cancer [31]. This team's evidence-based findings offer a unique approach. 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 germ line. It turns out to be very confusing as to how FSH acts on the ovary when an infertility expert treats a woman in clinic for egg collection or assisted reproduction. Does FSH really only play a survival role on ovarian follicles, preventing the cellular disappearance of a cohort of eggs when they begin to develop, or does FSH treatment apply a coordinated activity on ovarian stem cells, preventing cellular disappearance of a cohort of eggs when they begin to grow? or does the FSH treatment directly act on the ovarian stem cells and a whole new cohort of follicles assemble and start growing from the stem cells! We need better ways to interpret these well-kept mysteries of Mother Nature on the surface of the ovary. In humans, the process of initiating follicle maturation from the primordial pool is completely independent of gonadotropins. Although FSH is a primary factor regulating folliculogenesis, the “initial recruitment” of human PF is primarily controlled by factors synthesized in the ovaries [1]. Typically, FSH is secreted at high levels mid-cycle (preovulatory surge), but there is another, smaller factor. peak which occurs at the end of the luteal phase and is called the "intercycle peak" in humans or the "proestrus peak" (secondary surge) in rodents and is considered to be associated with the recruitment of follicles for the next cycle. Rani and Moudgal [60] showed that rather than the “preovulatory” FSH peak, the “proestrus” peak affects follicular growth and blocks ovulation during the following cycle. It is likely this intercycle spike in FSH that triggers stem cell activity in the OSE, leading to PF assembly [15] and these follicles then grow and mature rapidly. But more carefully planned studies need to be undertaken to generate more evidence to support this preliminary observation. Germ cell nest in adult ovaries A characteristic property of stem cell activity found in adult mammalian ovaries is the location of germ cell nests (cysts) [26]. In recent years, Zhang et al. [27], using 3 genetically modified adult mouse models, provided strong evidence critiquing 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 primordial follicles with de novo regenerated oocytes. Unlike their experiment where genetic manipulations are carried out to answer a biological question, Bhartiya's team used a more technical approach to give convincing answers to the same question of postnatal oogenesis (16). First, they characterized the..