Skip to main content
Top
Published in: Journal of Ovarian Research 1/2013

Open Access 01-12-2013 | Brief communication

Ovarian stem cells: absence of evidence is not evidence of absence

Authors: Deepa Bhartiya, Kalpana Sriraman, Seema Parte, Hiren Patel

Published in: Journal of Ovarian Research | Issue 1/2013

Login to get access

Abstract

Background

Lei and Spradling in a recent study published in PNAS failed to detect ‘germline cysts’ by elegant studies using lineage tracing approach and thus concluded that adult mouse ovaries lack stem cells. They proposed that primordial follicle pool generated during fetal life is sufficient to sustain oogenesis and that there is no renewal of oocytes during adult life. Contrary to their results, we have reported presence of very small pluripotent, embryonic-like stem cells (VSELs), their immediate descendants (OGSCs) and germ cell ‘cysts’ or ‘nests’ (formed by rapid cell division and incomplete cytokinesis) in surface epithelial cell smears of adult sheep, monkey and human ovaries.

Methods

In the present study, ovaries were collected from adult mouse (treated with 5 IU pregnant mare serum gonadotropin, PMSG) and sheep (from slaughter house) and testis from mouse treated with busulphan (25 mg/Kg). Ovarian surface epithelial (OSE) cells and testicular smears were studied for the presence of cysts. Sheep OSE smears were also used to show cytoplasmic continuity amongst the cyst cells studied by immunolocalization and confocal microscopy of stem cells specific markers OCT-4 and SSEA-4.

Results

Cysts were observed and confocal microscopy imaging confirmed cytoplasmic continuity amongst the cells comprising the cysts.

Conclusions

Cysts represent self-renewal and clonal expansion of stem cells with incomplete cytokinesis and are a hallmark feature of stem cells. We suggest the use of PMSG stimulated mouse ovaries and use of more primitive markers like OCT-4 or STELLA rather than MVH for lineage tracing studies to conclusively show presence of stem cells by lineage-tracing studies.
Appendix
Available only for authorised users
Literature
1.
go back to reference Lei L, Spradling AC: Female mice lack adult germ-line stem cells but sustain oogenesis using stable primordial follicles. Proc Natl Acad Sci U S A 2013, 110: 8585–8590. 10.1073/pnas.1306189110PubMedCentralPubMedCrossRef Lei L, Spradling AC: Female mice lack adult germ-line stem cells but sustain oogenesis using stable primordial follicles. Proc Natl Acad Sci U S A 2013, 110: 8585–8590. 10.1073/pnas.1306189110PubMedCentralPubMedCrossRef
2.
go back to reference Pepling ME: Follicular assembly: mechanisms of action. Reproduction 2012, 143: 139–149. 10.1530/REP-11-0299PubMedCrossRef Pepling ME: Follicular assembly: mechanisms of action. Reproduction 2012, 143: 139–149. 10.1530/REP-11-0299PubMedCrossRef
3.
go back to reference Lesch BJ, Page DC: Genetics of germ cell development. Nat Rev Genet 2012, 13: 781–794. 10.1038/nrg3294PubMedCrossRef Lesch BJ, Page DC: Genetics of germ cell development. Nat Rev Genet 2012, 13: 781–794. 10.1038/nrg3294PubMedCrossRef
4.
go back to reference Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL: Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 2004, 428: 145–150. 10.1038/nature02316PubMedCrossRef Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL: Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 2004, 428: 145–150. 10.1038/nature02316PubMedCrossRef
6.
go back to reference De Rosa L, De Luca M: Cell biology: dormant and restless skin stem cells. Nature 2012, 489: 215–217. 10.1038/489215aPubMedCrossRef De Rosa L, De Luca M: Cell biology: dormant and restless skin stem cells. Nature 2012, 489: 215–217. 10.1038/489215aPubMedCrossRef
7.
go back to reference Parte S, Bhartiya D, Telang J, Daithankar V, Salvi V, Zaveri K, Hinduja I: Detection, characterization, and spontaneous differentiation in vitro of very small embryonic-like putative stem cells in adult mammalian ovary. Stem Cells Dev 2011, 20: 1451–1464. 10.1089/scd.2010.0461PubMedCentralPubMedCrossRef Parte S, Bhartiya D, Telang J, Daithankar V, Salvi V, Zaveri K, Hinduja I: Detection, characterization, and spontaneous differentiation in vitro of very small embryonic-like putative stem cells in adult mammalian ovary. Stem Cells Dev 2011, 20: 1451–1464. 10.1089/scd.2010.0461PubMedCentralPubMedCrossRef
8.
go back to reference Bhartiya D, Sriraman K, Gunjal P, Modak H: Gonadotropin treatment augments postnatal oogenesis and primordial follicle assembly in adult mouse ovaries? J Ovarian Res 2012, 5: 32. 10.1186/1757-2215-5-32PubMedCentralPubMedCrossRef Bhartiya D, Sriraman K, Gunjal P, Modak H: Gonadotropin treatment augments postnatal oogenesis and primordial follicle assembly in adult mouse ovaries? J Ovarian Res 2012, 5: 32. 10.1186/1757-2215-5-32PubMedCentralPubMedCrossRef
9.
go back to reference Parte S, Bhartiya D, Manjramkar DD, Chauhan A, Joshi A: Stimulation of ovarian stem cells by follicle stimulating hormone and basic fibroblast growth factor during cortical tissue culture. J Ovarian Res 2013, 6: 20. 10.1186/1757-2215-6-20PubMedCentralPubMedCrossRef Parte S, Bhartiya D, Manjramkar DD, Chauhan A, Joshi A: Stimulation of ovarian stem cells by follicle stimulating hormone and basic fibroblast growth factor during cortical tissue culture. J Ovarian Res 2013, 6: 20. 10.1186/1757-2215-6-20PubMedCentralPubMedCrossRef
10.
go back to reference Patel H, Bhartiya D, Parte S, Gunjal P, Yedurkar S, Bhatt M: Follicle stimulating hormone modulates ovarian stem cells through alternately spliced receptor variant FSH-R3. J Ovarian Res 2013, 6: 52. 10.1186/1757-2215-6-52PubMedCentralPubMedCrossRef Patel H, Bhartiya D, Parte S, Gunjal P, Yedurkar S, Bhatt M: Follicle stimulating hormone modulates ovarian stem cells through alternately spliced receptor variant FSH-R3. J Ovarian Res 2013, 6: 52. 10.1186/1757-2215-6-52PubMedCentralPubMedCrossRef
11.
go back to reference Symonds DA, Tomic D, Miller KP, Flaws JA: Methoxychlor induces proliferation of the mouse ovarian surface epithelium. Toxicol Sci 2005, 83: 355–362.PubMedCrossRef Symonds DA, Tomic D, Miller KP, Flaws JA: Methoxychlor induces proliferation of the mouse ovarian surface epithelium. Toxicol Sci 2005, 83: 355–362.PubMedCrossRef
12.
13.
go back to reference Bhartiya D, Kasiviswanathan S, Unni SK, Pethe P, Dhabalia JV, Patwardhan S, Tongaonkar HB: Newer insights into premeiotic development of germ cells in adult human testis using Oct-4 as a stem cell marker. J Histochem Cytochem 2010, 58: 1093–1106. 10.1369/jhc.2010.956870PubMedCentralPubMedCrossRef Bhartiya D, Kasiviswanathan S, Unni SK, Pethe P, Dhabalia JV, Patwardhan S, Tongaonkar HB: Newer insights into premeiotic development of germ cells in adult human testis using Oct-4 as a stem cell marker. J Histochem Cytochem 2010, 58: 1093–1106. 10.1369/jhc.2010.956870PubMedCentralPubMedCrossRef
14.
go back to reference Bhartiya D, Sriraman K, Parte S: Stem cell interaction with somatic niche may hold the key to fertility restoration in cancer patients. Obstet Gynecol Int 2012, 2012: 921082.PubMedCentralPubMed Bhartiya D, Sriraman K, Parte S: Stem cell interaction with somatic niche may hold the key to fertility restoration in cancer patients. Obstet Gynecol Int 2012, 2012: 921082.PubMedCentralPubMed
15.
go back to reference Ratajczak MZ, Suszynska M, Pedziwiatr D, Mierzejewska K, Greco NJ: Umbilical cord blood-derived very small embryonic like stem cells (VSELs) as a source of pluripotent stem cells for regenerative medicine. Pediatr Endocrinol Rev 2012, 9: 639–643.PubMed Ratajczak MZ, Suszynska M, Pedziwiatr D, Mierzejewska K, Greco NJ: Umbilical cord blood-derived very small embryonic like stem cells (VSELs) as a source of pluripotent stem cells for regenerative medicine. Pediatr Endocrinol Rev 2012, 9: 639–643.PubMed
16.
go back to reference Bhartiya D, Shaikh A, Nagvenkar P, Kasiviswanathan S, Pethe P, Pawani H, Mohanty S, Rao SG, Zaveri K, Hinduja I: Very small embryonic-like stem cells with maximum regenerative potential get discarded during cord blood banking and bone marrow processing for autologous stem cell therapy. Stem Cells Dev 2012, 21: 1–6. 10.1089/scd.2011.0311PubMedCrossRef Bhartiya D, Shaikh A, Nagvenkar P, Kasiviswanathan S, Pethe P, Pawani H, Mohanty S, Rao SG, Zaveri K, Hinduja I: Very small embryonic-like stem cells with maximum regenerative potential get discarded during cord blood banking and bone marrow processing for autologous stem cell therapy. Stem Cells Dev 2012, 21: 1–6. 10.1089/scd.2011.0311PubMedCrossRef
17.
go back to reference Zhang D, Fouad H, Zoma WD, Salama SA, Wentz MJ, Al-Hendy A: Expression of stem and germ cell markers within nonfollicular structures in adult mouse ovary. Reprod Sci 2008, 15: 139–146. 10.1177/1933719107310708PubMedCrossRef Zhang D, Fouad H, Zoma WD, Salama SA, Wentz MJ, Al-Hendy A: Expression of stem and germ cell markers within nonfollicular structures in adult mouse ovary. Reprod Sci 2008, 15: 139–146. 10.1177/1933719107310708PubMedCrossRef
19.
go back to reference Park MR, Choi YJ, Kwon DN, Park C, Bui HT, Gurunathan S, Cho SG, Song H, Seo HG, Min G, Kim JH: Intraovarian transplantation of primordial follicles fails to rescue chemotherapy injured ovaries. Sci Rep 2013, 3: 1384.PubMedCentralPubMed Park MR, Choi YJ, Kwon DN, Park C, Bui HT, Gurunathan S, Cho SG, Song H, Seo HG, Min G, Kim JH: Intraovarian transplantation of primordial follicles fails to rescue chemotherapy injured ovaries. Sci Rep 2013, 3: 1384.PubMedCentralPubMed
20.
go back to reference Zhang H, Zheng W, Shen Y, Adhikari D, Ueno H, Liu K: Experimental evidence showing that no mitotically active female germline progenitors exist in postnatal mouse ovaries. Proc Natl Acad Sci U S A 2012, 109: 12580–12585. 10.1073/pnas.1206600109PubMedCentralPubMedCrossRef Zhang H, Zheng W, Shen Y, Adhikari D, Ueno H, Liu K: Experimental evidence showing that no mitotically active female germline progenitors exist in postnatal mouse ovaries. Proc Natl Acad Sci U S A 2012, 109: 12580–12585. 10.1073/pnas.1206600109PubMedCentralPubMedCrossRef
21.
go back to reference Gallardo T, Shirley L, John GB, Castrillon DH: Generation of a germ cell- specific mouse transgenic Cre line, Vasa-Cre. Genesis 2007, 45: 413–417. 10.1002/dvg.20310PubMedCentralPubMedCrossRef Gallardo T, Shirley L, John GB, Castrillon DH: Generation of a germ cell- specific mouse transgenic Cre line, Vasa-Cre. Genesis 2007, 45: 413–417. 10.1002/dvg.20310PubMedCentralPubMedCrossRef
22.
go back to reference Western PS, van den Bergen JA, Miles DC, Sinclair AH: Male fetal germ cell differentiation involves complex repression of the regulatory network controlling pluripotency. FASEB J 2010, 24: 3026–3035. 10.1096/fj.09-151555PubMedCrossRef Western PS, van den Bergen JA, Miles DC, Sinclair AH: Male fetal germ cell differentiation involves complex repression of the regulatory network controlling pluripotency. FASEB J 2010, 24: 3026–3035. 10.1096/fj.09-151555PubMedCrossRef
23.
go back to reference van den Bergen JA, Miles DC, Sinclair AH, Western PS: Normalizing gene expression levels in mouse fetal germ cells. Biol Reprod 2009, 81: 362–370. 10.1095/biolreprod.109.076224PubMedCentralPubMedCrossRef van den Bergen JA, Miles DC, Sinclair AH, Western PS: Normalizing gene expression levels in mouse fetal germ cells. Biol Reprod 2009, 81: 362–370. 10.1095/biolreprod.109.076224PubMedCentralPubMedCrossRef
24.
go back to reference Araki K, Imaizumi T, Okuyama K, Oike Y, Yamamura K: Efficiency of recombination by Cre transient expression in embryonic stem cells: comparison of various promoters. J Biochem 1997, 122: 977–982. 10.1093/oxfordjournals.jbchem.a021860PubMedCrossRef Araki K, Imaizumi T, Okuyama K, Oike Y, Yamamura K: Efficiency of recombination by Cre transient expression in embryonic stem cells: comparison of various promoters. J Biochem 1997, 122: 977–982. 10.1093/oxfordjournals.jbchem.a021860PubMedCrossRef
25.
go back to reference Tanaka SS, Toyooka Y, Akasu R, Katoh-Fukui Y, Nakahara Y, Suzuki R, Yokoyama M, Noce T: The mouse homolog of Drosophila vasa is required for the development of male germ cells. Genes Dev 2000, 14: 841–853.PubMedCentralPubMed Tanaka SS, Toyooka Y, Akasu R, Katoh-Fukui Y, Nakahara Y, Suzuki R, Yokoyama M, Noce T: The mouse homolog of Drosophila vasa is required for the development of male germ cells. Genes Dev 2000, 14: 841–853.PubMedCentralPubMed
26.
go back to reference Payer B, Saitou M, Barton SC, Thresher R, Dixon JP, Zahn D, Colledge WH, Carlton MB, Nakano T, Surani MA: Stella is a maternal effect gene required for normal early development in mice. Curr Biol 2003, 13: 2110–2117. 10.1016/j.cub.2003.11.026PubMedCrossRef Payer B, Saitou M, Barton SC, Thresher R, Dixon JP, Zahn D, Colledge WH, Carlton MB, Nakano T, Surani MA: Stella is a maternal effect gene required for normal early development in mice. Curr Biol 2003, 13: 2110–2117. 10.1016/j.cub.2003.11.026PubMedCrossRef
27.
go back to reference Woods DC, Tilly JL: An evolutionary perspective on adult female germline stem cell function from flies to humans. Semin Reprod Med 2013, 31: 24–32. 10.1055/s-0032-1331794PubMedCrossRef Woods DC, Tilly JL: An evolutionary perspective on adult female germline stem cell function from flies to humans. Semin Reprod Med 2013, 31: 24–32. 10.1055/s-0032-1331794PubMedCrossRef
28.
go back to reference Ratajczak MZ, Machalinski B, Wojakowski W, Ratajczak J, Kucia M: A hypothesis for an embryonic origin of pluripotent Oct-4(+) stem cells in adult bone marrow and other tissues. Leukemia 2007, 21: 860–867.PubMed Ratajczak MZ, Machalinski B, Wojakowski W, Ratajczak J, Kucia M: A hypothesis for an embryonic origin of pluripotent Oct-4(+) stem cells in adult bone marrow and other tissues. Leukemia 2007, 21: 860–867.PubMed
29.
go back to reference Massasa E, Costa XS, Taylor HS: Failure of the stem cell niche rather than loss of oocyte stem cells in the aging ovary. Aging (Albany NY) 2010, 2: 1–2. Massasa E, Costa XS, Taylor HS: Failure of the stem cell niche rather than loss of oocyte stem cells in the aging ovary. Aging (Albany NY) 2010, 2: 1–2.
Metadata
Title
Ovarian stem cells: absence of evidence is not evidence of absence
Authors
Deepa Bhartiya
Kalpana Sriraman
Seema Parte
Hiren Patel
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2013
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/1757-2215-6-65

Other articles of this Issue 1/2013

Journal of Ovarian Research 1/2013 Go to the issue