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Stem cells, progenitor cells, and lineage decisions in the ovary.

Hummitzsch K, Anderson RA, Wilhelm D, Wu J, Telfer EE, Russell DL, Robertson SA, Rodgers RJ - Endocr. Rev. (2014)

Bottom Line: Similarly, claims of very small embryonic-like cells are also preliminary.Surface epithelial cells originating from gonadal ridge epithelial-like cells and from the mesonephric epithelium at the hilum of the ovary have also been proposed.This review draws together the current evidence and perspectives on this topic.

View Article: PubMed Central - PubMed

Affiliation: Discipline of Obstetrics and Gynaecology (K.H., D.L.R., S.A.R., R.J.R.), School of Paediatrics and Reproductive Health, Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia 5005; Medical Research Council Centre for Reproductive Health (R.A.A.), The University of Edinburgh, The Queens Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom; Department of Anatomy and Developmental Biology (D.W.), Monash University, Clayton, Victoria, Australia 3800; Bio-X Institutes (J.W.), Shanghai Jiao Tong University, Shanghai 200240, China; and Institute of Cell Biology and Centre for Integrative Physiology (E.E.T), The University of Edinburgh, Edinburgh EH8 9XE, United Kingdom.

ABSTRACT
Exploring stem cells in the mammalian ovary has unleashed a Pandora's box of new insights and questions. Recent evidence supports the existence of stem cells of a number of the different cell types within the ovary. The evidence for a stem cell model producing mural granulosa cells and cumulus cells is strong, despite a limited number of reports. The recent identification of a precursor granulosa cell, the gonadal ridge epithelial-like cell, is exciting and novel. The identification of female germline (oogonial) stem cells is still very new and is currently limited to just a few species. Their origins and physiological roles, if any, are unknown, and their potential to produce oocytes and contribute to follicle formation in vivo lacks robust evidence. The precursor of thecal cells remains elusive, and more compelling data are needed. Similarly, claims of very small embryonic-like cells are also preliminary. Surface epithelial cells originating from gonadal ridge epithelial-like cells and from the mesonephric epithelium at the hilum of the ovary have also been proposed. Another important issue is the role of the stroma in guiding the formation of the ovary, ovigerous cords, follicles, and surface epithelium. Immune cells may also play key roles in developmental patterning, given their critical roles in corpora lutea formation and regression. Thus, while the cellular biology of the ovary is extremely important for its major endocrine and fertility roles, there is much still to be discovered. This review draws together the current evidence and perspectives on this topic.

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Schematic diagram of the proposed development and repair of ovarian surface epithelium. A, In early fetal ovarian development, the ovarian surface epithelium (OSE) in the hilum region is derived from the mesonephros, whereas the remaining surface of ovary is covered by GREL cells, which later differentiate to surface epithelial cells or granulosa cells. [Adapted from K. Hummitzsch et al: A new model of development of the mammalian ovary and follicles. PloS One. 2013;8:e55578 (31).] B, Flesken-Nikitin et al identified an ALDH-, LGR5-, LEF-1-, CD133-, and CK6B-expressing stem cell niche in the hilum region of adult mice ovaries, which is responsible for the OSE repair after ovulation and is susceptible to malignant transformation. [Adapted from A. Flesken-Nikitin et al: Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche. Nature. 2013;495:241–245 (136).] C, A recent study in adult mice identified LGR5-positive OSE stem cells not only in the hilum region but also along the remaining ovarian surface as small clusters, mainly near ovulating follicles and on the apical side of corpora lutea. [Adapted from A. Ng et al: Lgr5 marks stem/progenitor cells in ovary and tubal epithelia. Nat Cell Biol. 2014;16:745–757 (137).] Abbreviations: ALDH, aldehyde dehydrogenase; LEF1, lymphoid enhancer-binding factor 1; CD133, cluster of differentiation 133; CK6B, cytokeratin 6B.
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Figure 5: Schematic diagram of the proposed development and repair of ovarian surface epithelium. A, In early fetal ovarian development, the ovarian surface epithelium (OSE) in the hilum region is derived from the mesonephros, whereas the remaining surface of ovary is covered by GREL cells, which later differentiate to surface epithelial cells or granulosa cells. [Adapted from K. Hummitzsch et al: A new model of development of the mammalian ovary and follicles. PloS One. 2013;8:e55578 (31).] B, Flesken-Nikitin et al identified an ALDH-, LGR5-, LEF-1-, CD133-, and CK6B-expressing stem cell niche in the hilum region of adult mice ovaries, which is responsible for the OSE repair after ovulation and is susceptible to malignant transformation. [Adapted from A. Flesken-Nikitin et al: Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche. Nature. 2013;495:241–245 (136).] C, A recent study in adult mice identified LGR5-positive OSE stem cells not only in the hilum region but also along the remaining ovarian surface as small clusters, mainly near ovulating follicles and on the apical side of corpora lutea. [Adapted from A. Ng et al: Lgr5 marks stem/progenitor cells in ovary and tubal epithelia. Nat Cell Biol. 2014;16:745–757 (137).] Abbreviations: ALDH, aldehyde dehydrogenase; LEF1, lymphoid enhancer-binding factor 1; CD133, cluster of differentiation 133; CK6B, cytokeratin 6B.

Mentions: The mature ovary is covered by a single layer of flat to cuboidal epithelial cells, the surface epithelium. This layer constantly undergoes morphological changes, particularly during the repair of the ovarian surface after the rupture of the follicle wall during ovulation (130). The physiology of ovarian surface epithelium; its regulation by hormones, growth factors, and cytokines; and its involvement in the ovulatory process have been reviewed previously (131–133), and Figure 5 illustrates more recent theories about the origins of these cells.


Stem cells, progenitor cells, and lineage decisions in the ovary.

Hummitzsch K, Anderson RA, Wilhelm D, Wu J, Telfer EE, Russell DL, Robertson SA, Rodgers RJ - Endocr. Rev. (2014)

Schematic diagram of the proposed development and repair of ovarian surface epithelium. A, In early fetal ovarian development, the ovarian surface epithelium (OSE) in the hilum region is derived from the mesonephros, whereas the remaining surface of ovary is covered by GREL cells, which later differentiate to surface epithelial cells or granulosa cells. [Adapted from K. Hummitzsch et al: A new model of development of the mammalian ovary and follicles. PloS One. 2013;8:e55578 (31).] B, Flesken-Nikitin et al identified an ALDH-, LGR5-, LEF-1-, CD133-, and CK6B-expressing stem cell niche in the hilum region of adult mice ovaries, which is responsible for the OSE repair after ovulation and is susceptible to malignant transformation. [Adapted from A. Flesken-Nikitin et al: Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche. Nature. 2013;495:241–245 (136).] C, A recent study in adult mice identified LGR5-positive OSE stem cells not only in the hilum region but also along the remaining ovarian surface as small clusters, mainly near ovulating follicles and on the apical side of corpora lutea. [Adapted from A. Ng et al: Lgr5 marks stem/progenitor cells in ovary and tubal epithelia. Nat Cell Biol. 2014;16:745–757 (137).] Abbreviations: ALDH, aldehyde dehydrogenase; LEF1, lymphoid enhancer-binding factor 1; CD133, cluster of differentiation 133; CK6B, cytokeratin 6B.
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Related In: Results  -  Collection

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Figure 5: Schematic diagram of the proposed development and repair of ovarian surface epithelium. A, In early fetal ovarian development, the ovarian surface epithelium (OSE) in the hilum region is derived from the mesonephros, whereas the remaining surface of ovary is covered by GREL cells, which later differentiate to surface epithelial cells or granulosa cells. [Adapted from K. Hummitzsch et al: A new model of development of the mammalian ovary and follicles. PloS One. 2013;8:e55578 (31).] B, Flesken-Nikitin et al identified an ALDH-, LGR5-, LEF-1-, CD133-, and CK6B-expressing stem cell niche in the hilum region of adult mice ovaries, which is responsible for the OSE repair after ovulation and is susceptible to malignant transformation. [Adapted from A. Flesken-Nikitin et al: Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche. Nature. 2013;495:241–245 (136).] C, A recent study in adult mice identified LGR5-positive OSE stem cells not only in the hilum region but also along the remaining ovarian surface as small clusters, mainly near ovulating follicles and on the apical side of corpora lutea. [Adapted from A. Ng et al: Lgr5 marks stem/progenitor cells in ovary and tubal epithelia. Nat Cell Biol. 2014;16:745–757 (137).] Abbreviations: ALDH, aldehyde dehydrogenase; LEF1, lymphoid enhancer-binding factor 1; CD133, cluster of differentiation 133; CK6B, cytokeratin 6B.
Mentions: The mature ovary is covered by a single layer of flat to cuboidal epithelial cells, the surface epithelium. This layer constantly undergoes morphological changes, particularly during the repair of the ovarian surface after the rupture of the follicle wall during ovulation (130). The physiology of ovarian surface epithelium; its regulation by hormones, growth factors, and cytokines; and its involvement in the ovulatory process have been reviewed previously (131–133), and Figure 5 illustrates more recent theories about the origins of these cells.

Bottom Line: Similarly, claims of very small embryonic-like cells are also preliminary.Surface epithelial cells originating from gonadal ridge epithelial-like cells and from the mesonephric epithelium at the hilum of the ovary have also been proposed.This review draws together the current evidence and perspectives on this topic.

View Article: PubMed Central - PubMed

Affiliation: Discipline of Obstetrics and Gynaecology (K.H., D.L.R., S.A.R., R.J.R.), School of Paediatrics and Reproductive Health, Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia 5005; Medical Research Council Centre for Reproductive Health (R.A.A.), The University of Edinburgh, The Queens Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom; Department of Anatomy and Developmental Biology (D.W.), Monash University, Clayton, Victoria, Australia 3800; Bio-X Institutes (J.W.), Shanghai Jiao Tong University, Shanghai 200240, China; and Institute of Cell Biology and Centre for Integrative Physiology (E.E.T), The University of Edinburgh, Edinburgh EH8 9XE, United Kingdom.

ABSTRACT
Exploring stem cells in the mammalian ovary has unleashed a Pandora's box of new insights and questions. Recent evidence supports the existence of stem cells of a number of the different cell types within the ovary. The evidence for a stem cell model producing mural granulosa cells and cumulus cells is strong, despite a limited number of reports. The recent identification of a precursor granulosa cell, the gonadal ridge epithelial-like cell, is exciting and novel. The identification of female germline (oogonial) stem cells is still very new and is currently limited to just a few species. Their origins and physiological roles, if any, are unknown, and their potential to produce oocytes and contribute to follicle formation in vivo lacks robust evidence. The precursor of thecal cells remains elusive, and more compelling data are needed. Similarly, claims of very small embryonic-like cells are also preliminary. Surface epithelial cells originating from gonadal ridge epithelial-like cells and from the mesonephric epithelium at the hilum of the ovary have also been proposed. Another important issue is the role of the stroma in guiding the formation of the ovary, ovigerous cords, follicles, and surface epithelium. Immune cells may also play key roles in developmental patterning, given their critical roles in corpora lutea formation and regression. Thus, while the cellular biology of the ovary is extremely important for its major endocrine and fertility roles, there is much still to be discovered. This review draws together the current evidence and perspectives on this topic.

Show MeSH
Related in: MedlinePlus