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Table 1 Pivotal observations advanced in support of presence of stem cells in ovarian surface epithelium of mammalian species

From: Germline cells in ovarian surface epithelium of mammalians: a promising notion

Published studies Study observations Interpretation of published data
Johnson et al., (2004) [9] Highly expression of early meiotic markers in surface epithelium of postnatal ovary. Formation of chimeric follicles after transplantation of wild type ovarian tissue onto ovary of GFP expressing transgenic mice. The regeneration of de novo new primordial follicle suggest that oocytes may arise from a rare uncharacterized population of cells, which are present in BM and peripheral circulation
Johnson et al. (2005) [10] Bone marrow serves as a source of germ stem cells in adult mammalian, which can be transported by peripheral blood to the ovaries. Induction of oocyte atresia by gonadotoxic agents possibly mobilized VSELs from BM to enter peripheral circulation
Bukovsky et al. (2004, 2005, 2009, 2011, 2012) [29, 30, 3335] Putative germ cells within the OSE of postnatal ovary differentiate from mesenchymal progenitors in the ovarian tunica albuginea. Large oocyte-like cells expressing zona pellucida proteins are formed in set up cell cultures from scrapped OSE. Reproducible, oocyte-like cells from OSE of ovaries subjected to ovotoxic agents. These results are in agreement with previous data that stem cells in OSE are able to produce oocyte-like structures [38, 39]
Virant-Klun et al. (2008, 2008, 2011) [38, 39, 42] VSEL in OSE able to generate oocyte-like cells in vitro. These cells expressed pluripotent specific markers. Oocytes derived from VSEL cells de novo underwent parthenogenetic activation to produce blastocyst-like cells with neuronal phenotype and embryoid bodies. These structures expressed pluripotent specific markers Oct-4, Oct-4 A, Nanog, Sox-2, and TERT. Presence of rare putative stem cells with germline characteristics in the OSE of postmenopausal women accorded the initial finding of existence of GSC in adult mouse ovary [9].
Zhang et al. (2008) [37] Germ cell markers (OCT-3/4, MVH, SCF-R and SSEA-1) and meiotic markers (DMC1 and SCP3) within specific cells aggregated from the periphery of adult murine ovaries. Mixed cluster of committed stem cells and also a transitional stage of GSC that may retain the capacity of proliferation and differentiation.
Niikura et al. (2009) [44] Aged mouse ovaries are able to form premeiotic germ cells (high expression of Stra8 and Daz1), when transfer into a young ovarian environment, they can differentiate into oocytes (increased expression of Oct4-GFP, c-kit, Mvh and SSEA-1). The concept of rapid decline in the number of follicles being mainly due to decreased oocyte renewal rather than to an accelerated loss.
Zou et al. (2009) [45] MVH positive FGSCs isolated from adult mice ovaries and retained in vitro for months. These cells after transplantation into atretic ovaries of recipient mice by gonadotoxic agents produced new follicle, which fertilized and gave rise to offspring carrying the same gene as their mothers. This study purified the initial cells expressing germ cell markers, but not early stem cell markers.
Parte et al. (2011) [41] Two different populations of putative stem cells detected in scrapped OSE of postnatal mammalian ovary, namely VSELs and slightly larger ovarian stem cells termed as OGSCs. VSELs expressed nuclear Oct-4 but the OGSCs exhibited cytoplasmic Oct-4. Pluripotent specific markers were detected in human and sheep OSE. After 3 weeks of OSE cultures, oocyte-like cells expressing c-kit, DAZL, VASA and ZP4 emerged VSELs are totipotent to pluripotent in nature and form OGSCs, which are able to further differentiate into oocyte-like and neuronal-like structures.
Santiquet et al. (2012) [11] Chemotherapy sterilized SCID mice could not generate new oocytes after BMT but fertility of mice has improved. Despite ovarian atresia by chemotherapeutics, sparing follicles could be restored of self-tolerance of ovarian antigens; thereby, BM cells possibly initiate an endocrine/paracrine signal that improves the functionality of ovarian niche.
Bhartiya et al. (2012) [43, 46] Gonadotropin induced pluripotent VSELs underwent proliferation and differentiation (increased expression of stella, fragilis, total Oct-4, Vasa and MVH). Differentiating oocyte undergoes to meiosis and exhibits germ cell markers like Stra-8, Scp3 and Dmc1. Close association of developing oocytes with mesenchymal cells in vitro, which is produced by epithelial to mesenchymal transition of the OSE suggested that new oocytes surrounded by granulosa-like cells assemble as primordial follicles in the OSE of adult ovary.
White et al. (2012) [47] Purified rare mitotically active cells features in both mouse and human ovaries, generated oocytes (diameter of 35 – 50 micron) per se and entered into meiotic division. Injection of GFP transfected human OSCs into the human ovarian cortical tissue strips resulted in generation of GFP expressing follicles one-two weeks after xenografting these strips into diabetic SCID mice. Successfully purified rare cell surface DDX4 positive OGCs from cortical tissue of reproductive aged adult human ovaries. The study showed that rare cells (expression of cell-surface of DDX4) exist in the OSCs of adult human. Production of chimeric follicle in vitro and more importantly in vivo when injected into cortical tissue strips from human ovaries.
Hayashi et al. (2012) [48] After transplantation of both female PGCs and embryonic gonadal somatic cells under ovarian bursa or kidney capsules of recipient mice, induced-ESCs transformed into PGCLCs, which contributes to oocyte-like cells in reconstituted ovaries. These cells matured into fully functional germinal vesicle stage, including multiple layers of granulosa and theca cells in vivo. This study demonstrated that possibility of reconstitute female germline development in vitro, not only in mice, but also in humans.