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

Virant‐Klun, Irma; Skutella, Thomas; Štimpfel, Martin; Šinkovec, Jasna

doi:10.1155/2011/381928

Cited by 55 publications

(63 citation statements)

References 49 publications

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“…2D) and mesonephric ( Fig. 2A) somatic cells were immunonegative at all stages examined, as was the ovarian surface epithelium, despite recent reports of the isolation of LIN28-positive germ cell-like cells from the adult ovarian surface epithelium [30], and the expression of LIN28 by a subpopulation of epithelial ovarian cancer cells [31]. Negative controls also displayed no staining (Fig.…”

Section: Stem Cells and Developmentmentioning

confidence: 82%

LIN28 Is Selectively Expressed by Primordial and Pre-Meiotic Germ Cells in the Human Fetal Ovary

Childs

Kinnell

et al. 2012

Stem Cells and Development

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Germ cell development requires timely transition from primordial germ cell (PGC) self-renewal to meiotic differentiation. This is associated with widespread changes in gene expression, including downregulation of stem cell-associated genes, such as OCT4 and KIT, and upregulation of markers of germ cell differentiation and meiosis, such as VASA, STRA8, and SYCP3. The stem cell-expressed RNA-binding protein Lin28 has recently been demonstrated to be essential for PGC specification in mice, and LIN28 is expressed in human germ cell tumors with phenotypic similarities to human fetal germ cells. We have therefore examined the expression of LIN28 during normal germ cell development in the human fetal ovary, from the PGC stage, through meiosis to the initiation of follicle formation. LIN28 transcript levels were highest when the gonad contained only PGCs, and decreased significantly with increasing gestation, coincident with the onset of germ cell differentiation. Immunohistochemistry revealed LIN28 protein expression to be germ cell-specific at all stages examined. All PGCs expressed LIN28, but at later gestations expression was restricted to a subpopulation of germ cells, which we demonstrate to be primordial and premeiotic germ cells based on immunofluorescent colocalization of LIN28 and OCT4, and absence of overlap with the meiosis marker SYCP3. We also demonstrate the expression of the LIN28 target precursor pri-microRNA transcripts pri-LET7a/f/d and pri-LET-7g in the human fetal ovary, and that expression of these is highest at the PGC stage, mirroring that of LIN28. The spatial and temporal restriction of LIN28 expression and coincident peaks of expression of LIN28 and target pri-microRNAs suggest important roles for this protein in the maintenance of the germline stem cell state and the regulation of microRNA activity in the developing human ovary.

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Section: Stem Cells and Developmentmentioning

confidence: 82%

LIN28 Is Selectively Expressed by Primordial and Pre-Meiotic Germ Cells in the Human Fetal Ovary

Childs

Kinnell

et al. 2012

Stem Cells and Development

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“…Immunostaining of ovaries from 7 days, 2 month and 20 months old mice were performed according to previously published procedures [8]. The primary antibodies used in this study were as follows: anti-MVH (1:100, ab27591), anti-OCT4 (1:100, ab18976), anti-YAP1 (1:100, ab56701), anti-LATS2 (1:100, ab54073), and anti-MST1 (1:100, ab51134).…”

Section: Methodsmentioning

confidence: 99%

“…Based on the rates of oocyte atresia and clearance, these germ cells are needed to continuously replenish the follicle pool. Currently, several research groups have demonstrated the isolation of germline stem cells from the ovarian surface epithelium (OSE) of adult and even menopausal mouse and human ovaries [8,9,10] and have also successfully isolated and characterized long-term cultured ovarian germline stem cells (OGSCs) from neonatal and adult mouse ovaries [11,12,13,14,15,16,17]. However, the OSE layer has also been confirmed to be a normal, naturally present source of oocytes by producing stem cells in the embryonic or fetal period of life, and it is commonly referred to as the ‘‘germinal'' epithelium [18].…”

Section: Introductionmentioning

confidence: 99%

Ovarian Germline Stem Cells (OGSCs) and the Hippo Signaling Pathway Association with Physiological and Pathological Ovarian Aging in Mice

Zhou

Zheng

et al. 2015

Cell Physiol Biochem

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Background: The Hippo signaling pathway plays fundamental roles in stem cell maintenance in a variety of tissues and has thus implications for stem cell biology. Key components of this recently discovered pathway have been shown to be associated with primordial follicle activation. However, whether the Hippo signaling pathway plays a role in the development of Ovarian Germline Stem Cells (OGSCs) during physiological and pathological ovarian aging in mice is unknown. Methods: Mice at the age of 7 days (7D), or of 2, 10, or 20 months (2M, 10M, 20M) and mice at 2M treated with TPT and CY/BUS drugs were selected as physiological and pathological ovarian aging models, respectively. Immunohistochemistry was used to assess the development of follicles, and the co-localization of genes characteristic of OGSCs with MST1, LATS2 and YAP1 was assessed by immunofluorescence, western blotting and real-time PCR methods. Results: The Hippo signal pathway and MVH/OCT4 genes were co-expressed in the mouse ovarian cortex. The level and co-localization of LATS2, MST1, MVH, and OCT4 were significantly decreased with increased age, but YAP1 was more prevalent in the mouse ovarian cortex of 2M mice than 7D mice and was not observed in 20M mice. Furthermore, YAP1, MVH, and OCT4 were gradually decreased after TPT and CY/BUS treatment, and LATS2 mRNA and protein up-regulation persisted in TPT- and CY/BUS-treated mice. However, the expression of MST1 was lower in the TPT and CY/BUS groups compared with the control group. In addition, pYAP1 protein showed the highest expression in the ovarian cortexes of 7D mice compared with 20M mice, and the value of pYAP1/YAP1 decreased from 7D to 20M. Moreover, pYAP1 decreased in the TPT- and CY/BUS-treated groups, but the value of pYAP1/YAP1 increased in these groups. Conclusion: Taken together, our results show that the Hippo signaling pathway is associated with the changes that take place in OGSCs during physiological and pathological ovarian aging in mice. Thus, the Hippo signaling pathway may be involved in the development schedule of OGSCs.

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“…Putative stem cells were found in the adult ovarian surface epithelium of different mammals, including humans [61,[78][79][80], in mouse ovarian stroma [21] and in the theca layer [29], which surrounds the developing follicle.…”

Section: Expression Of Stem Cell Markers In Granulosa Cells From Follmentioning

confidence: 99%

Plasticity of granulosa cells: on the crossroad of stemness and transdifferentiation potential

Dzafic

Štimpfel

Virant‐Klun

2013

J Assist Reprod Genet

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The ovarian follicle represents the basic functional unit of the ovary and consists of an oocyte, which is surrounded by granulosa cells (GCs). GCs play an important role in the growth and development of the follicle. They are subject to increased attention since it has recently been shown that the subpopulation of GCs within the growing follicle possesses exceptionally plasticity showing stem cell characteristics. In assisted reproduction programs, oocytes are retrieved from patients together with GCs, which are currently discarded daily, but could be an interesting subject to be researched and potentially used in regenerative medicine in the future. Isolated GCs expressed stem cell markers such as OCT-4, NANOG and SOX-2, showed high telomerase activity, and were in vitro differentiated into other cell types, otherwise not present within ovarian follicles. Recently another phenomenon demonstrated in GCs is transdifferentiation, which could explain many ovarian pathological conditions. Possible applications in regenerative medicine are also given.

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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

Cited by 55 publications

References 49 publications

LIN28 Is Selectively Expressed by Primordial and Pre-Meiotic Germ Cells in the Human Fetal Ovary

LIN28 Is Selectively Expressed by Primordial and Pre-Meiotic Germ Cells in the Human Fetal Ovary

Ovarian Germline Stem Cells (OGSCs) and the Hippo Signaling Pathway Association with Physiological and Pathological Ovarian Aging in Mice

Plasticity of granulosa cells: on the crossroad of stemness and transdifferentiation potential

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