NDLI: VSELs and OSCs together sustain oogenesis in adult ovaries and their dysfunction results in age-related senescence, PCOS, POI and cancer

Content Provider	Springer Nature : BioMed Central
Author	Bhartiya, Deepa Sharma, Diksha
Abstract	Multiple studies using single-cell RNA sequencing (scRNAseq) have failed to detect stem cells in adult ovaries. We have maintained that two populations of ovarian stem cells including pluripotent, very small embryonic-like stem cells (VSELs) and tissue-committed ‘progenitors’ termed ovarian stem cells (OSCs) can easily be detected in Hematoxylin and Eosin-stained ovary surface epithelial (OSE) cells smears prepared from both mice and human ovaries. Most likely the stem cells never get subjected to scRNAseq since they pellet down only by centrifuging cells suspension at 1000 g while cells for scRNAseq were invariably prepared by centrifuging at 200-400 g. A recent article provided further explanation for the failure of scRNAseq to detect ovarian stem cells. Extensive reanalysis of data (generated by scRNAseq) using an advanced software successfully detected OSCs and meiotic markers supporting neo-oogenesis in adult human ovaries. But this article remained critical on the biological relevance of VSELs and their relationship with OSCs. By carefully studying the OSE cells smears (which hold VSELs, OSCs and germ cell nests GCNs), prepared by partial trypsin digestion of intact mice ovaries during different stages of estrus cycle, we have successfully delineated novel functions of VSELs/OSCs in vivo under physiological conditions. VSELs undergo asymmetrical divisions to self-renew and give rise to slightly bigger OSCs which in turn undergo symmetrical divisions and clonal expansion to form GCNs, regular neo-oogenesis and follicle assembly. GCNs have been earlier described in fetal ovaries and during OSE cells culture (from adult ovaries) in response to FSH treatment. Dysfunction of VSELs/OSCs (which express ERα, ERβ, FSHR) due to neonatal exposure to endocrine disruption results in ovarian insufficiency and polycystic ovaries. VSELs have also been implicated in ovarian cancer. Age-related ovarian senescence/menopause is also due to dysfunction and blocked differentiation of VSELs/OSCs. These novel findings in vivo along with abundant in vitro and lineage tracing studies data in published literature provides huge scope for further research, offers novel avenues to manage ovarian pathologies and calls for re-writing of textbooks.
Related Links	https://ovarianresearch.biomedcentral.com/counter/pdf/10.1186/s13048-022-01093-y.pdf
Ending Page	6
Page Count	6
Starting Page	1
File Format	HTM / HTML
ISSN	17572215
DOI	10.1186/s13048-022-01093-y
Journal	Journal of Ovarian Research
Issue Number	1
Volume Number	16
Language	English
Publisher	BioMed Central
Publisher Date	2023-02-01
Access Restriction	Open
Subject Keyword	Gynecology Reproductive Medicine Ovary Stem cells Ovary surface epithelium Very small embryonic-like stem cells (VSELs) Ovarian stem cells (OSCs) Germ cell nests
Content Type	Text
Resource Type	Article
Subject	Oncology Obstetrics and Gynecology
Journal Impact Factor	3.8/2023
5-Year Journal Impact Factor	4.2/2023

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Correction: VSELs and OSCs together sustain oogenesis in adult ovaries and their dysfunction results in age-related senescence, PCOS, POI and cancer

Aged mice ovaries harbor stem cells and germ cell nests but fail to form follicles

Ovary does harbor stem cells - size of the cells matter!

Ovarian stem cells are always accompanied by very small embryonic-like stem cells in adult mammalian ovary

Small putative NANOG, SOX2, and SSEA-4-positive stem cells resembling very small embryonic-like stem cells in sections of ovarian tissue in patients with ovarian cancer

RETRACTED ARTICLE: Extremely Active Nano-formulation of Resveratrol (XAR™) attenuates and reverses chemotherapy-induced damage in mice ovaries and testes

Positive effects of prolonged caloric restriction on the population of very small embryonic-like stem cells – hematopoietic and ovarian implications

Differential expression of pluripotent and germ cell markers in ovarian surface epithelium according to age in female mice

Gonadotropin treatment augments postnatal oogenesis and primordial follicle assembly in adult mouse ovaries?

VSELs and OSCs together sustain oogenesis in adult ovaries and their dysfunction results in age-related senescence, PCOS, POI and cancer

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Correction: VSELs and OSCs together sustain oogenesis in adult ovaries and their dysfunction results in age-related senescence, PCOS, POI and cancer

Aged mice ovaries harbor stem cells and germ cell nests but fail to form follicles

Ovary does harbor stem cells - size of the cells matter!

Ovarian stem cells are always accompanied by very small embryonic-like stem cells in adult mammalian ovary

Small putative NANOG, SOX2, and SSEA-4-positive stem cells resembling very small embryonic-like stem cells in sections of ovarian tissue in patients with ovarian cancer

RETRACTED ARTICLE: Extremely Active Nano-formulation of Resveratrol (XAR™) attenuates and reverses chemotherapy-induced damage in mice ovaries and testes

Positive effects of prolonged caloric restriction on the population of very small embryonic-like stem cells – hematopoietic and ovarian implications

Differential expression of pluripotent and germ cell markers in ovarian surface epithelium according to age in female mice

Gonadotropin treatment augments postnatal oogenesis and primordial follicle assembly in adult mouse ovaries?

VSELs and OSCs together sustain oogenesis in adult ovaries and their dysfunction results in age-related senescence, PCOS, POI and cancer