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      Ovarian Surface Epithelium in Patients with Severe Ovarian Infertility: A Potential Source of Cells Expressing Markers of Pluripotent/Multipotent Stem Cells

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          Abstract

          The aim of this study was to confirm the presence of stem cells in the ovarian surface epithelium of patients with premature ovarian failure and no mature follicles and oocytes. In these patients, small round cells of unknown origin expressing SOX-2 marker of pluripotency were observed among the epithelial cells just after the ovarian surface epithelium scraping. These cells were an integral part of the ovarian surface epithelium. When the scraped cells were cultured in a medium with added follicular fluid to provide some ovarian niche, primitive oocyte-like cells and typical round-shaped cell clusters positively stained on alkaline phosphatase, and markers of pluripotency, such as SOX-2 and SSEA-4, were developed. These markers were expressed early and also later in the culture. Single oocyte-like cells expressed genes OCT4A, SOX-2, NANOG, NANOS, STELLA, CD9, LIN28, KLF4, GDF3, and MYC, characteristic for pluripotent stem cells. The results of this study confirmed the presence of putative stem cells in the ovarian surface epithelium of these patients and provided some basis to create a stem cell line in the future.

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          Production of offspring from a germline stem cell line derived from neonatal ovaries.

          Kang Zou, Zhe Yuan, Zhaojuan Yang … (2009)
          The idea that females of most mammalian species have lost the capacity for oocyte production at birth has been challenged recently by the finding that juvenile and adult mouse ovaries possess mitotically active germ cells. However, the existence of female germline stem cells (FGSCs) in postnatal mammalian ovaries still remains a controversial issue among reproductive biologists and stem cell researchers. We have now established a neonatal mouse FGSC line, with normal karyotype and high telomerase activity, by immunomagnetic isolation and culture for more than 15 months. FGSCs from adult mice were isolated and cultured for more than 6 months. These FGSCs were infected with GFP virus and transplanted into ovaries of infertile mice. Transplanted cells underwent oogenesis and the mice produced offspring that had the GFP transgene. These findings contribute to basic research into oogenesis and stem cell self-renewal and open up new possibilities for use of FGSCs in biotechnology and medicine.
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            Estrogen production and action

            Linda R. Nelson, Serdar Bulun (2001)
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              Detection, characterization, and spontaneous differentiation in vitro of very small embryonic-like putative stem cells in adult mammalian ovary.

              Jyoti Telang, Vinita Daithankar, Indira Hinduja … (2011)
              The present study was undertaken to detect, characterize, and study differentiation potential of stem cells in adult rabbit, sheep, monkey, and menopausal human ovarian surface epithelium (OSE). Two distinct populations of putative stem cells (PSCs) of variable size were detected in scraped OSE, one being smaller and other similar in size to the surrounding red blood cells in the scraped OSE. The smaller 1-3 μm very small embryonic-like PSCs were pluripotent in nature with nuclear Oct-4 and cell surface SSEA-4, whereas the bigger 4-7 μm cells with cytoplasmic localization of Oct-4 and minimal expression of SSEA-4 were possibly the tissue committed progenitor stem cells. Pluripotent gene transcripts of Oct-4, Oct-4A, Nanog, Sox-2, TERT, and Stat-3 in human and sheep OSE were detected by reverse transcriptase-polymerase chain reaction. The PSCs underwent spontaneous differentiation into oocyte-like structures, parthenote-like structures, embryoid body-like structures, cells with neuronal-like phenotype, and embryonic stem cell-like colonies, whereas the epithelial cells transformed into mesenchymal phenotype by epithelial-mesenchymal transition in 3 weeks of OSE culture. Germ cell markers like c-Kit, DAZL, GDF-9, VASA, and ZP4 were immuno-localized in oocyte-like structures. In conclusion, as opposed to the existing view of OSE being a bipotent source of oocytes and granulosa cells, mammalian ovaries harbor distinct very small embryonic-like PSCs and tissue committed progenitor stem cells population that have the potential to develop into oocyte-like structures in vitro, whereas mesenchymal fibroblasts appear to form supporting granulosa-like somatic cells. Research at the single-cell level, including complete gene expression profiling, is required to further confirm whether postnatal oogenesis is a conserved phenomenon in adult mammals.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Biomed Biotechnol
                Journal ID (publisher-id): JBB
                Title: Journal of Biomedicine and Biotechnology
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 1110-7243
                ISSN (Electronic): 1110-7251
                Publication date (Print): 2011
                Publication date (Electronic): 6 December 2011
                Volume: 2011
                Electronic Location Identifier: 381928
                Affiliations
                1Department of Obstetrics and Gynecology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
                2Institute for Anatomy and Cell Biology, Faculty of Medicine, University of Heidelberg, 69120 Heidelberg, Germany
                Author notes
                *Irma Virant-Klun: irma.virant@ 123456kclj.si

                Academic Editor: Matthew B. Wheeler

                Article
                DOI: 10.1155/2011/381928
                PMC ID: 3237017
                PubMed ID: 22187524
                SO-VID: 9fc94630-a3ea-40a8-ba73-cbd1eda9fbd7
                Copyright © Copyright © 2011 Irma Virant-Klun et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 6 June 2011
                Date accepted : 31 August 2011
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Molecular medicine
                Data availability:
                ScienceOpen disciplines: Molecular medicine

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