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Table 1 Critical approaches with pros and cons

From: Used protocols for isolation and propagation of ovarian stem cells, different cells with different traits




Johnson et al., 2004 [6]

Johnson et al., 2005 [21]

OSCs originate at a site extraneous to the ovary, namely the bone marrow, and are transported to the ovary via the circulatory system

Eggan, 2006 [56]

By designing of a parabiotic mouse models showed that no evidence

For bone marrow cells, or any other normally circulating cells, contribute to the formation of mature, ovulated oocytes.

Tilly et al., 2007 [57]

He believed that Eggan focused solely on eggs retrieved from the oviducts following superovulation and did not include the outcome of evaluating the ovaries of their recipient mice for donor-derived immature oocytes.

Begum, 2008 [58]

No evidence was found to support the hypothesis that progenitor cells from extra-ovarian sources can repopulate the adult ovary. The findings are consistent with the conventional view that a limited number of oocytes are formed before birth and declines with age.

Lee et al., 2007 [59]

They claimed that bone marrow transplantation rescued long-term fertility in CTx-treated females, but all offspring were derived from the recipient germline.

Parte et al. [33, 37, 38]

Bhartiya et al., [3436]

They believed that OSCs are originating from VSELs.

Johnson et al., 2004 [6]

Bukovsky, 2005 [25]

Johnson et al., 2005 [21]

Zou et al., 2009 [18]

OSCs are present in post natal mammalian ovary and are actively contributing in folliculogenesis and neo-oogenesis

Bristol-Gould et al., 2006 [60]

By designing of a mathematical model of the dynamics of follicle progression, they indicated that no germline stem cells could be identified by SSEA-1 immunostaining.

Tilly et al., [61]

Tilly et al., [57]

Confirmed their previous results

Malcolm Faddy, 2009 [62]

Gosden et al., [63]

They believed that new finding might be based on spurious results.

Kerr et al., [7]

They found no evidence for ovarian germline stem cells, their data support the hypothesis of postnatal follicle renewal in postnatal and adult ovaries of C57BL/6 mice.

Wallace [64]

By mathematical modelling of the ovarian reserve found no

evidence to support the occurrence of neo-oogenesis in humans

Abban et al., [65]

They not only confirmed zou’s experimental results, but also they predict that FGSC arises between the border of PGC and oogonia development and the initiation of germline cysts.

Byskov et al., [32]

Using some histological and immunohistochemistry evaluations and based on previous observations claimed that the results presented by Johnson et al. (2004) [6] cannot support the concept of neo-oogenesis in the postnatal mouse ovary. Nor does there exist any evidence for neo-folliculogenesis in the adult mammalian ovary.

Others, [14, 19, 26, 44, 48, 50, 6673]

Liu et al. 2007 [74]

They showed that We show that active meiosis, neo-oogenesis and GSCs are unlikely to exist in normal, adult, human ovaries. No early meiotic-specific or oogenesis-associated mRNAs for SPO11, PRDM9, SCP1, TERT and NOBOX were detectable in adult human ovaries using RT–PCR

Zhang et al., 2012 [75]

By producing a multiple fluorescent Rosa26rbw/+;Ddx4-Cre germline reporter mouse model for in vivo and in vitro tracing of the development of female germline cell lineage, they showed that no mitotically active female germline progenitors exist in postnatal mouse ovaries

Lei et al., 2013 [76]

Using sensitive lineage labeling system to determine whether stem cells are needed in female adult mice to compensate for follicular losses and to directly identify active germ-line stem cells, they showe that Female mice lack adult germ-line stem cells but sustain oogenesis using stable primordial follicles

Johnson et al., 2004 [6]

Positive BrdU Mitotic germ cells in ovarian epithelium

Elena Notarianni, 2011 [77]

BrdU-incorporation arose from either mitochondrial (mt) DNA replication or DNA repair in oocytes, on the basis that “the degree of BrdU incorporation observed in cells due to either of these processes is several log orders less than that seen during replication of the nuclear genome during mitosis.


Bukovsky and Virant Klun [25, 27]

Cultured OSE gives rise to “oocyte-like” cells

Mvh + germ cells located in the OSE

“Oocyte-like” phenotype of cells in OSE derived cultures

Other observation

Elena Notarianni, 2011 [77]

These cells are actually undergoing apoptosis, necrosis or oncosis.

Oocytes in transit across the OSE during exfoliation.

Nondescript cells undergoing oncosis

Reinterpretation of results by Notarianni


White et al., 2012 [19]

Woods et al. 2013 [20]

Successful isolation of OSCs using DDX4 marker via FACS

Hernandez et al., 2015 [23]

Zhang et al., 2015 [78]

They were able to isolated a population of cells from the human ovarian cell preparation

However, THEY did not detect any DDX4 mRNA expression by qPCR in these cells. They believed that the isolated cells bound tightly to the DDX4-specific antibody in FACS and became ‘DDX4-positive’ after culture. So use of the DDX4-specific antibody in FACS is not suitable for specifically selecting for a certain type of cell that expresses DDX4.

Park et al., 2014 [73]

Woods et al., 2015 [22]

Confirmed their previous results