Aged mice ovaries harbor stem cells and germ cell nests but fail to form follicles
Abstract Background We recently published evidence to suggest that two populations of stem cells including very small embryonic-like stem cells (VSELs) and ovarian stem cells (OSCs) in ovary surface epithelium (OSE) undergo proliferation/differentiation, germ cell nests (GCN) formation, meiosis and...
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| Format: | Article |
| Language: | English |
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BMC
2022-03-01
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| Series: | Journal of Ovarian Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13048-022-00968-4 |
| _version_ | 1828716742748143616 |
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| author | Diksha Sharma Deepa Bhartiya |
| author_facet | Diksha Sharma Deepa Bhartiya |
| author_sort | Diksha Sharma |
| collection | DOAJ |
| description | Abstract Background We recently published evidence to suggest that two populations of stem cells including very small embryonic-like stem cells (VSELs) and ovarian stem cells (OSCs) in ovary surface epithelium (OSE) undergo proliferation/differentiation, germ cell nests (GCN) formation, meiosis and eventually differentiate into oocytes that assemble as primordial follicles on regular basis during estrus cycle. Despite presence of stem cells, follicles get exhausted with advancing age in mice and result in senescence equivalent to menopause in women. Stem cells in aged ovaries can differentiate into oocytes upon transplantation into young ovaries, however, it is still not well understood why follicles get depleted with advancing age despite the presence of stem cells. The aim of the present study was to study stem cells and GCN in aged ovaries. Methods OSE cells from aged mice (> 18 months equivalent to > 55 years old women) were enzymatically separated and used to study stem cells. Viable (7-AAD negative) VSELs in the size range of 2–6 µm with a surface phenotype of Lin−CD45−Sca-1+ were enumerated by flow cytometry. Immuno-fluorescence and RT-PCR analysis were done to study stem/progenitor cells (OCT-4, MVH, SCP3) and transcripts specific for VSELs (Oct-4A, Sox-2, Nanog), primordial germ cells (Stella), germ cells (Oct-4, Mvh), early meiosis (Mlh1, Scp1) and ring canals (Tex14). Results Putative VSELs and OSCs were detected as darkly stained, spherical cells with high nucleo-cytoplasmic ratio along with germ cells nests (GCN) in Hematoxylin & Eosin stained OSE cells smears. Germ cells in GCN with distinct cytoplasmic continuity expressed OCT-4, MVH and SCP3. Transcripts specific for stem cells, early meiosis and ring canals were detected by RT-PCR studies. Conclusion Rather than resulting as a consequence of accelerated loss of primordial follicle and their subsequent depletion, ovarian senescence/menopause occurs as a result of stem cells dysfunction. VSELs and OSCs exist along with increased numbers of GCNs arrested in pre-meiotic or early meiotic stage in aged ovaries and primordial follicle assembly is blocked possibly due to age-related changes in their microenvironment. |
| first_indexed | 2024-03-12T14:16:54Z |
| format | Article |
| id | doaj.art-cc9fae7dcb2a45d88e1096924e56c855 |
| institution | Directory Open Access Journal |
| issn | 1757-2215 |
| language | English |
| last_indexed | 2024-03-12T14:16:54Z |
| publishDate | 2022-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj.art-cc9fae7dcb2a45d88e1096924e56c8552023-08-20T11:18:49ZengBMCJournal of Ovarian Research1757-22152022-03-0115111310.1186/s13048-022-00968-4Aged mice ovaries harbor stem cells and germ cell nests but fail to form folliclesDiksha Sharma0Deepa Bhartiya1Stem Cell Biology Department, ICMR- National Institute for Research in Reproductive HealthStem Cell Biology Department, ICMR- National Institute for Research in Reproductive HealthAbstract Background We recently published evidence to suggest that two populations of stem cells including very small embryonic-like stem cells (VSELs) and ovarian stem cells (OSCs) in ovary surface epithelium (OSE) undergo proliferation/differentiation, germ cell nests (GCN) formation, meiosis and eventually differentiate into oocytes that assemble as primordial follicles on regular basis during estrus cycle. Despite presence of stem cells, follicles get exhausted with advancing age in mice and result in senescence equivalent to menopause in women. Stem cells in aged ovaries can differentiate into oocytes upon transplantation into young ovaries, however, it is still not well understood why follicles get depleted with advancing age despite the presence of stem cells. The aim of the present study was to study stem cells and GCN in aged ovaries. Methods OSE cells from aged mice (> 18 months equivalent to > 55 years old women) were enzymatically separated and used to study stem cells. Viable (7-AAD negative) VSELs in the size range of 2–6 µm with a surface phenotype of Lin−CD45−Sca-1+ were enumerated by flow cytometry. Immuno-fluorescence and RT-PCR analysis were done to study stem/progenitor cells (OCT-4, MVH, SCP3) and transcripts specific for VSELs (Oct-4A, Sox-2, Nanog), primordial germ cells (Stella), germ cells (Oct-4, Mvh), early meiosis (Mlh1, Scp1) and ring canals (Tex14). Results Putative VSELs and OSCs were detected as darkly stained, spherical cells with high nucleo-cytoplasmic ratio along with germ cells nests (GCN) in Hematoxylin & Eosin stained OSE cells smears. Germ cells in GCN with distinct cytoplasmic continuity expressed OCT-4, MVH and SCP3. Transcripts specific for stem cells, early meiosis and ring canals were detected by RT-PCR studies. Conclusion Rather than resulting as a consequence of accelerated loss of primordial follicle and their subsequent depletion, ovarian senescence/menopause occurs as a result of stem cells dysfunction. VSELs and OSCs exist along with increased numbers of GCNs arrested in pre-meiotic or early meiotic stage in aged ovaries and primordial follicle assembly is blocked possibly due to age-related changes in their microenvironment.https://doi.org/10.1186/s13048-022-00968-4OvaryStem cellsGerm cell nestVSELsOSCsAgeing |
| spellingShingle | Diksha Sharma Deepa Bhartiya Aged mice ovaries harbor stem cells and germ cell nests but fail to form follicles Journal of Ovarian Research Ovary Stem cells Germ cell nest VSELs OSCs Ageing |
| title | Aged mice ovaries harbor stem cells and germ cell nests but fail to form follicles |
| title_full | Aged mice ovaries harbor stem cells and germ cell nests but fail to form follicles |
| title_fullStr | Aged mice ovaries harbor stem cells and germ cell nests but fail to form follicles |
| title_full_unstemmed | Aged mice ovaries harbor stem cells and germ cell nests but fail to form follicles |
| title_short | Aged mice ovaries harbor stem cells and germ cell nests but fail to form follicles |
| title_sort | aged mice ovaries harbor stem cells and germ cell nests but fail to form follicles |
| topic | Ovary Stem cells Germ cell nest VSELs OSCs Ageing |
| url | https://doi.org/10.1186/s13048-022-00968-4 |
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