The Experts below are selected from a list of 819 Experts worldwide ranked by ideXlab platform
Jerry Pelletier - One of the best experts on this subject based on the ideXlab platform.
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The Wilms' tumor suppressor gene (wt1) product regulates Dax-1 gene expression during Gonadal differentiation.
Molecular and cellular biology, 1999Co-Authors: Jungho Kim, Dirk Prawitt, Nabeel Bardeesy, Elena Torban, Caroline Vicaner, Paul Goodyer, Bernard Zabel, Jerry PelletierAbstract:Gonadal differentiation is dependent upon a molecular cascade responsible for ovarian or testicular development from the bipotential Gonadal Ridge. Genetic analysis has implicated a number of gene products essential for this process, which include Sry, WT1, SF-1, and DAX-1. We have sought to better define the role of WT1 in this process by identifying downstream targets of WT1 during normal Gonadal development. We have noticed that in the developing murine Gonadal Ridge, wt1 expression precedes expression of Dax-1, a nuclear receptor gene. We document here that the spatial distribution profiles of both proteins in the developing gonad overlap. We also demonstrate that WT1 can activate the Dax-1 promoter. Footprinting analysis, transient transfections, promoter mutagenesis, and mobility shift assays suggest that WT1 regulates Dax-1 via GC-rich binding sites found upstream of the Dax-1 TATA box. We show that two WT1-interacting proteins, the product of a Denys-Drash syndrome allele of wt1 and prostate apoptosis response-4 protein, inhibit WT1-mediated transactivation of Dax-1. In addition, we demonstrate that WT1 can activate the endogenous Dax-1 promoter. Our results indicate that the WT1–DAX-1 pathway is an early event in the process of mammalian sex determination.
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Abnormal Gonadal differentiation in two subjects with ambiguous genitalia, Mullerian structures, and normally developed testes: Evidence for a defect in Gonadal Ridge development
Human genetics, 1996Co-Authors: J. S. Fuqua, Jerry Pelletier, Ellen S. Sher, Elizabeth J. Perlman, Maria D. Urban, Majid Ghahremani, Claude J. Migeon, Terry R. Brown, Gary D. BerkovitzAbstract:Among a group of patients with abnormal sexual differentiation, we have identified two subjects who had a 46,XY karyotype, ambiguous genitalia, and well-developed Mullerian structures, but normal appearing testes. The presence of ambiguous genitalia and persistent Mullerian structures implied both Leydig cell and Sertoli cell dysfunction, hence, Gonadal dysgenesis. However, the normal testicular histology suggested that the underlying abnormality was not a defect in testis determination itself but an abnormality in timing of Gonadal Ridge and testis development. In one of the two subjects genomic DNA was available. The sequence of the SRY gene was normal. Because rare patients with partial androgen insensitivity may have a similar phenotype, the AR gene was evaluated by denaturing gradient gel electrophoresis (DGGE) and was normal. Some subjects with mutation of the WT1 gene or with deletion of the distal short arm of chromosome 9 may have similar phenotypes. The WT1 gene was studied by single-strand conformation polymorphism (SSCP) analysis and was normal. In addition, there was no loss of heterozygosity of polymorphic markers in distal 9p. The gene for Mullerian inhibiting substance (MIS) was also studied by SSCP and was normal. Although the exact mechanism for the defect in the two subjects is unknown, it may be due to an abnormality in a gene or genes involved in the timing of Gonadal Ridge development.
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WT1 mutations contribute to abnormal genital system development and hereditary Wilms' tumour
Nature, 1991Co-Authors: Jerry Pelletier, Thomas M Glaser, Daniel A. Haber, Wendy Bruening, David E. HousmanAbstract:WILMS' tumour (WT), aniridia, genitourinary abnormalities and mental retardation form a symptom group (WAGR syndrome) associated with hemizygous deletions of DNA in chromosome band 11p13 (refs 1,2). However, it has not been clear whether hemizygosity at a single locus contributes to more than one phenotype. The tumour suppressor gene for Wilms' tumour, WT1, has been characterized3,4: it is expressed at high levels in the glomeruli of the kidney5, as well as the Gonadal Ridge of the developing gonad5, the Sertoli cells of the testis6 and the epithelial and granulosa cells of the ovary6, suggesting a developmental role in the genital system in addition to the kidney. We now report constitutional mutations within the WT1 genes of two individuals with a combination of WT and genital abnormalities as evidence of a role for a recessive oncogene in mammalian development.
Etsuro Yamaha - One of the best experts on this subject based on the ideXlab platform.
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The origin and migration of primordial germ cells in sturgeons.
PloS one, 2014Co-Authors: Taiju Saito, Katsutoshi Arai, Martin Pšenička, Rie Goto, Shinji Adachi, Kunio Inoue, Etsuro YamahaAbstract:Primordial germ cells (PGCs) arise elsewhere in the embryo and migrate into developing Gonadal Ridges during embryonic development. In several model animals, formation and migration patterns of PGCs have been studied, and it is known that these patterns vary. Sturgeons (genus Acipenser) have great potential for comparative and evolutionary studies of development. Sturgeons belong to the super class Actinoptergii, and their developmental pattern is similar to that of amphibians, although their phylogenetic position is an out-group to teleost fishes. Here, we reveal an injection technique for sturgeon eggs allowing visualization of germplasm and PGCs. Using this technique, we demonstrate that the PGCs are generated at the vegetal pole of the egg and they migrate on the yolky cell mass toward the Gonadal Ridge. We also provide evidence showing that PGCs are specified by inheritance of maternally supplied germplasm. Furthermore, we demonstrate that the migratory mechanism is well-conserved between sturgeon and other remotely related teleosts, such as goldfish, by a single PGCs transplantation (SPT) assay. The mode of PGCs specification in sturgeon is similar to that of anurans, but the migration pattern resembles that of teleosts.
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The lineage of a single blastomere at the vegetal pole at blastula stage.
2014Co-Authors: Taiju Saito, Katsutoshi Arai, Martin Pšenička, Rie Goto, Shinji Adachi, Kunio Inoue, Etsuro YamahaAbstract:(A) The blastula stage embryo with a labeled blastomere with FITC (arrowhead). The upper figure shows the bright view and the lower figure the fluorescent view. (B) The labeled embryo at stage 32. PGCs were located in positions where gonads are expected to develop, apart from the main part of the labeled region. (C) The labeled embryo at 3 weeks post-fertilization. After fry started feeding, PGCs still could be observed at the Gonadal Ridge of the embryo. The scale bars indicate 500 µm.
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A schematic illustration of development of sturgeon PGCs during embryonic development.
2014Co-Authors: Taiju Saito, Katsutoshi Arai, Martin Pšenička, Rie Goto, Shinji Adachi, Kunio Inoue, Etsuro YamahaAbstract:(A) 1-cell stage. (B) Early cleavage stage. (C) Gastrula stage: a cross-section cut along animal-vegetal axis. (D) Neurula stage: a cross-section cut along animal-vegetal axis. (E) Closed neural tube stage: posterior lateral view. (F) 4-dpf embryo: lateral view. (G) 5-dpf embryo: lateral view. The regions colored gray show the position labeled by GFP or FITC-dextran injected at the vegetal pole of an early-stage embryo. The red regions in (A) and (B) show the embryonic area where germplasm was observed by TEM. Red dots in (C) and (D) are presumptive PGCs. PGCs were difficult to observe as a single cell, since the PGCs still remained in a group of GFP/FITC positive vegetal cells at this stage. Red dots in (E–G) are PGCs in migration. At stage (E), PGCs showed the crescent-like localization on the yolky cells around the posterior part of the embryonic body. Around stage (E) to (F), PGCs exhibited active movements with the cellular protrusions. After stage (G), however, most PGCs transformed into a round shape and were passively moved toward the Gonadal Ridge via the mesenchyme.
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The Origin and Migration of Primordial Germ Cells in
2013Co-Authors: Taiju Saito, Katsutoshi Arai, Rie Goto, Shinji Adachi, Kunio Inoue, Etsuro YamahaAbstract:Primordial germ cells (PGCs) arise elsewhere in the embryo and migrate into developing Gonadal Ridges during embryonic development. In several model animals, formation and migration patterns of PGCs have been studied, and it is known that these patterns vary. Sturgeons (genus Acipenser) have great potential for comparative and evolutionary studies of development. Sturgeons belong to the super class Actinoptergii, and their developmental pattern is similar to that of amphibians, although their phylogenetic position is an out-group to teleost fishes. Here, we reveal an injection technique for sturgeon eggs allowing visualization of germplasm and PGCs. Using this technique, we demonstrate that the PGCs are generated at the vegetal pole of the egg and they migrate on the yolky cell mass toward the Gonadal Ridge. We also provide evidence showing that PGCs are specified by inheritance of maternally supplied germplasm. Furthermore, we demonstrate that the migratory mechanism is well-conserved between sturgeon and other remotely related teleosts, such as goldfish, by a single PGCs transplantation (SPT) assay. The mode of PGCs specification in sturgeon is similar to that of anurans, but th
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Generation of germ-line chimera zebrafish using primordial germ cells isolated from cultured blastomeres and cryopreserved embryoids
The International journal of developmental biology, 2010Co-Authors: Yutaka Kawakami, Rie Goto-kazeto, Taiju Saito, Takafumi Fujimoto, Shogo Higaki, Yoshiyuki Takahashi, Katsutoshi Arai, Etsuro YamahaAbstract:Primordial germ cells (PGCs) are the only cells in developing embryos with the potential to transmit genetic information to the next generation. In our previous study, a single PGC transplanted into a host differentiated into fertile gametes and produced germ-line chimeras of cyprinid fish, including zebrafish. In this study, we aimed to induce germ-line chimeras by transplanting donor PGCs from various sources (normal embryos at different stages, dissociated blastomeres, embryoids, or embryoids cryopreserved by vitrification) into host blastulae, and compare the migration rates of the PGCs towards the Gonadal Ridge. Isolated, cultured blastomeres not subject to mesodermal induction were able to differentiate into PGCs that retained their motility. Moreover, these PGCs successfully migrated towards the Gonadal Ridge of the host and formed viable gametes. Motility depended on developmental stage and culture duration: PGCs obtained at earlier developmental stages and with shorter cultivation periods showed an increased rate of migration to the Gonadal Ridge. Offspring were obtained from natural spawning between normal females and chimeric males. These results provide the basis for new methods of gene preservation in zebrafish.
David E. Housman - One of the best experts on this subject based on the ideXlab platform.
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WT1 mutations contribute to abnormal genital system development and hereditary Wilms' tumour
Nature, 1991Co-Authors: Jerry Pelletier, Thomas M Glaser, Daniel A. Haber, Wendy Bruening, David E. HousmanAbstract:WILMS' tumour (WT), aniridia, genitourinary abnormalities and mental retardation form a symptom group (WAGR syndrome) associated with hemizygous deletions of DNA in chromosome band 11p13 (refs 1,2). However, it has not been clear whether hemizygosity at a single locus contributes to more than one phenotype. The tumour suppressor gene for Wilms' tumour, WT1, has been characterized3,4: it is expressed at high levels in the glomeruli of the kidney5, as well as the Gonadal Ridge of the developing gonad5, the Sertoli cells of the testis6 and the epithelial and granulosa cells of the ovary6, suggesting a developmental role in the genital system in addition to the kidney. We now report constitutional mutations within the WT1 genes of two individuals with a combination of WT and genital abnormalities as evidence of a role for a recessive oncogene in mammalian development.
Raymond J Rodgers - One of the best experts on this subject based on the ideXlab platform.
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morphometric analyses and gene expression related to germ cells Gonadal Ridge epithelial like cells and granulosa cells during development of the bovine fetal ovary
PLOS ONE, 2019Co-Authors: Katja Hummitzsch, Nicholas Hatzirodos, Helen F Irvingrodgers, Monica D Hartanti, Viv E A Perry, Richard A Anderson, Raymond J RodgersAbstract:Cells on the surface of the mesonephros give rise to replicating Gonadal Ridge Epithelial-Like (GREL) cells, the first somatic cells of the Gonadal Ridge. Later germ cells associate with the GREL cells in the ovigerous cords, and the GREL cells subsequently give rise to the granulosa cells in follicles. To examine these events further, 27 bovine fetal ovaries of different gestational ages were collected and prepared for immunohistochemical localisation of collagen type I and Ki67 to identify regions of the ovary and cell proliferation, respectively. The non-stromal cortical areas (collagen-negative) containing GREL cells and germ cells and later in development, the follicles with oocytes and granulosa cells, were analysed morphometrically. Another set of ovaries (n = 17) were collected and the expression of genes associated with germ cell lineages and GREL/granulosa cells were quantitated by RT-PCR. The total volume of non-stromal areas in the cortex increased significantly and progressively with ovarian development, plateauing at the time the surface epithelium developed. However, the proportion of non-stromal areas in the cortex declined significantly and progressively throughout gestation, largely due to a cessation in growth of the non-stroma cells and the continued growth of stroma. The proliferation index in the non-stromal area was very high initially and then declined substantially at the time follicles formed. Thereafter, it remained low. The numerical density of the non-stromal cells was relatively constant throughout ovarian development. The expression levels of a number of genes across gestation either increased (AMH, FSHR, ESR1, INHBA), declined (CYP19A1, ESR2, ALDH1A1, DSG2, OCT4, LGR5) or showed no particular pattern (CCND2, CTNNB1, DAZL, FOXL2, GATA4, IGFBP3, KRT19, NR5A1, RARRES1, VASA, WNT2B). Many of the genes whose expression changed across gestation, were positively or negatively correlated with each other. The relationships between these genes may reflect their roles in the important events such as the transition of ovigerous cords to follicles, oogonia to oocytes or GREL cells to granulosa cells.
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Development of the Mammalian Ovary and Follicles
The Ovary, 2019Co-Authors: Katja Hummitzsch, Helen F. Irving-rodgers, Jeffrey Schwartz, Raymond J RodgersAbstract:Abstract During embryonic development, the Gonadal Ridge/ovarian primordium is formed by proliferation of the recently described Gonadal Ridge epithelial-like (GREL) cells at the surface epithelium of the mesonephros. Primordial germ cells (PGCs) migrate into the ovarian primordium, and stroma from the underlying mesonephros begins to penetrate the primordium. This results in partitioning of the developing ovary into irregularly shaped ovigerous cords composed of GREL cells and PGCs/oogonia. The cords are always separated from the stroma by a basal lamina, and the stroma expands laterally below the outermost layers of GREL cells forming a subepithelial basal lamina, establishing an epithelial-stromal interface. Subsequently, a mature surface epithelium develops from the GREL cells on the surface of the ovary primordium. Expansion of the stroma continues to partition the ovigerous cords into smaller groups of cells, eventually forming follicles. These contain an oocyte surrounded by GREL cells, which become granulosa cells, all enclosed by a basal lamina. Thus, ovarian surface epithelial cells and granulosa cells are both derived from GREL cells.
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A New Model of Development of the Mammalian Ovary and
2016Co-Authors: Katja Hummitzsch, Nicholas Hatzirodos, Dagmar Wilhelm, Helen F. Irving-rodgers, Wendy Bonner, Laetitia Sabatier, Dieter P. Reinhardt, Yoshikazu Sado, Yoshifumi Ninomiya, Raymond J RodgersAbstract:Ovarian follicular granulosa cells surround and nurture oocytes, and produce sex steroid hormones. It is believed that during development the ovarian surface epithelial cells penetrate into the ovary and develop into granulosa cells when associating with oogonia to form follicles. Using bovine fetal ovaries (n = 80) we identified a novel cell type, termed GREL for Gonadal Ridge Epithelial-Like. Using 26 markers for GREL and other cells and extracellular matrix we conducted immunohisto-chemistry and electron microscopy and chronologically tracked all somatic cell types during development. Before 70 days of gestation the Gonadal Ridge/ovarian primordium is formed by proliferation of GREL cells at the surface epithelium of the mesonephros. Primordial germ cells (PGCs) migrate into the ovarian primordium. After 70 days, stroma from the underlying mesonephros begins to penetrate the primordium, partitioning the developing ovary into irregularly-shaped ovigerous cords composed of GREL cells and PGCs/oogonia. Importantly we identified that the cords are always separated from the stroma by a basal lamina. Around 130 days of gestation the stroma expands laterally below the outermost layers of GREL cells forming a sub-epithelial basal lamina and establishing an epithelial-stromal interface. It is at this stage that a mature surface epithelium develops from the GREL cells on the surface of the ovary primordium. Expansion of the stroma continue
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Stem Cells, Progenitor Cells, and Lineage Decisions in the Ovary
Endocrine reviews, 2014Co-Authors: Katja Hummitzsch, Richard A Anderson, Dagmar Wilhelm, Evelyn E. Telfer, Darryl L. Russell, Sarah A. Robertson, Raymond J RodgersAbstract: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 mesoneph...
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Schematic diagram of ovarian development.
2013Co-Authors: Katja Hummitzsch, Nicholas Hatzirodos, Dagmar Wilhelm, Helen F. Irving-rodgers, Wendy Bonner, Laetitia Sabatier, Dieter P. Reinhardt, Yoshikazu Sado, Yoshifumi Ninomiya, Raymond J RodgersAbstract:(A) The development of the ovary commences at the mesonephric surface epithelium (yellow cells) in the location of the future Gonadal Ridge. (B) Some mesonephric surface epithelial cells change phenotype into GREL cells (yellow-blue cells). (C) The GREL cells proliferate and the basal lamina underlying the mesonephric surface epithelium breaks down allowing stromal cells (green) to penetrate into the Gonadal Ridge. (D) GREL cells continue to proliferate and PGCs (grey) migrate into the Ridge between the GREL cells. Mesonephric stroma including vasculature (red) continues to penetrate and expand in the ovary. (E) Oogonia proliferate and stroma penetrates further towards the ovarian surface enclosing oogonia and GREL cells into ovigerous cords. The cords are surrounded by a basal lamina at their interface with stroma, but are open to the ovarian surface. Stromal areas including those between the ovigerous cords contain capillaries. (F) A compartmentalization into cortex and medulla becomes obvious. The cortex is characterised by alternating areas of ovigerous cords and stroma, whereas the medulla is formed by stromal cells, vasculature and tubules originating from the mesonephros (rete ovarii). Once stroma penetrates below the cells on the surface it spreads laterally. The GREL cells at the surface are then aligned by a basal lamina at their interface with the stroma and begin to differentiate into typical ovarian surface epithelium (yellow cells). Some germ cells at the surface are also compartmentalized to the surface as stroma expands below it. (G) Ovigerous cords are partitioned into smaller cords and eventually into follicles. These contain GREL cells that form granulosa cells (blue cells) and oogonia that form oocytes. The first primordial follicles appear in the inner cortex-medulla region, surrounded by a basal lamina. A now fully intact basal lamina underlies multiple layers of surface epithelial cells. (H) At the final stage the surface epithelium becomes mostly single-layered and a tunica albuginea, densely packed with fibres, develops from the stroma below the surface epithelial basal lamina. Some primordial follicles become activated and commence development into primary and preantral follicles.
Katja Hummitzsch - One of the best experts on this subject based on the ideXlab platform.
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morphometric analyses and gene expression related to germ cells Gonadal Ridge epithelial like cells and granulosa cells during development of the bovine fetal ovary
PLOS ONE, 2019Co-Authors: Katja Hummitzsch, Nicholas Hatzirodos, Helen F Irvingrodgers, Monica D Hartanti, Viv E A Perry, Richard A Anderson, Raymond J RodgersAbstract:Cells on the surface of the mesonephros give rise to replicating Gonadal Ridge Epithelial-Like (GREL) cells, the first somatic cells of the Gonadal Ridge. Later germ cells associate with the GREL cells in the ovigerous cords, and the GREL cells subsequently give rise to the granulosa cells in follicles. To examine these events further, 27 bovine fetal ovaries of different gestational ages were collected and prepared for immunohistochemical localisation of collagen type I and Ki67 to identify regions of the ovary and cell proliferation, respectively. The non-stromal cortical areas (collagen-negative) containing GREL cells and germ cells and later in development, the follicles with oocytes and granulosa cells, were analysed morphometrically. Another set of ovaries (n = 17) were collected and the expression of genes associated with germ cell lineages and GREL/granulosa cells were quantitated by RT-PCR. The total volume of non-stromal areas in the cortex increased significantly and progressively with ovarian development, plateauing at the time the surface epithelium developed. However, the proportion of non-stromal areas in the cortex declined significantly and progressively throughout gestation, largely due to a cessation in growth of the non-stroma cells and the continued growth of stroma. The proliferation index in the non-stromal area was very high initially and then declined substantially at the time follicles formed. Thereafter, it remained low. The numerical density of the non-stromal cells was relatively constant throughout ovarian development. The expression levels of a number of genes across gestation either increased (AMH, FSHR, ESR1, INHBA), declined (CYP19A1, ESR2, ALDH1A1, DSG2, OCT4, LGR5) or showed no particular pattern (CCND2, CTNNB1, DAZL, FOXL2, GATA4, IGFBP3, KRT19, NR5A1, RARRES1, VASA, WNT2B). Many of the genes whose expression changed across gestation, were positively or negatively correlated with each other. The relationships between these genes may reflect their roles in the important events such as the transition of ovigerous cords to follicles, oogonia to oocytes or GREL cells to granulosa cells.
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Development of the Mammalian Ovary and Follicles
The Ovary, 2019Co-Authors: Katja Hummitzsch, Helen F. Irving-rodgers, Jeffrey Schwartz, Raymond J RodgersAbstract:Abstract During embryonic development, the Gonadal Ridge/ovarian primordium is formed by proliferation of the recently described Gonadal Ridge epithelial-like (GREL) cells at the surface epithelium of the mesonephros. Primordial germ cells (PGCs) migrate into the ovarian primordium, and stroma from the underlying mesonephros begins to penetrate the primordium. This results in partitioning of the developing ovary into irregularly shaped ovigerous cords composed of GREL cells and PGCs/oogonia. The cords are always separated from the stroma by a basal lamina, and the stroma expands laterally below the outermost layers of GREL cells forming a subepithelial basal lamina, establishing an epithelial-stromal interface. Subsequently, a mature surface epithelium develops from the GREL cells on the surface of the ovary primordium. Expansion of the stroma continues to partition the ovigerous cords into smaller groups of cells, eventually forming follicles. These contain an oocyte surrounded by GREL cells, which become granulosa cells, all enclosed by a basal lamina. Thus, ovarian surface epithelial cells and granulosa cells are both derived from GREL cells.
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A New Model of Development of the Mammalian Ovary and
2016Co-Authors: Katja Hummitzsch, Nicholas Hatzirodos, Dagmar Wilhelm, Helen F. Irving-rodgers, Wendy Bonner, Laetitia Sabatier, Dieter P. Reinhardt, Yoshikazu Sado, Yoshifumi Ninomiya, Raymond J RodgersAbstract:Ovarian follicular granulosa cells surround and nurture oocytes, and produce sex steroid hormones. It is believed that during development the ovarian surface epithelial cells penetrate into the ovary and develop into granulosa cells when associating with oogonia to form follicles. Using bovine fetal ovaries (n = 80) we identified a novel cell type, termed GREL for Gonadal Ridge Epithelial-Like. Using 26 markers for GREL and other cells and extracellular matrix we conducted immunohisto-chemistry and electron microscopy and chronologically tracked all somatic cell types during development. Before 70 days of gestation the Gonadal Ridge/ovarian primordium is formed by proliferation of GREL cells at the surface epithelium of the mesonephros. Primordial germ cells (PGCs) migrate into the ovarian primordium. After 70 days, stroma from the underlying mesonephros begins to penetrate the primordium, partitioning the developing ovary into irregularly-shaped ovigerous cords composed of GREL cells and PGCs/oogonia. Importantly we identified that the cords are always separated from the stroma by a basal lamina. Around 130 days of gestation the stroma expands laterally below the outermost layers of GREL cells forming a sub-epithelial basal lamina and establishing an epithelial-stromal interface. It is at this stage that a mature surface epithelium develops from the GREL cells on the surface of the ovary primordium. Expansion of the stroma continue
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Stem Cells, Progenitor Cells, and Lineage Decisions in the Ovary
Endocrine reviews, 2014Co-Authors: Katja Hummitzsch, Richard A Anderson, Dagmar Wilhelm, Evelyn E. Telfer, Darryl L. Russell, Sarah A. Robertson, Raymond J RodgersAbstract: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 mesoneph...
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a new model of development of the mammalian ovary and follicles
PLOS ONE, 2013Co-Authors: Katja Hummitzsch, Nicholas Hatzirodos, Helen F Irvingrodgers, Wendy Bonner, Laetitia Sabatier, Dieter P. Reinhardt, Yoshikazu Sado, Yoshifumi Ninomiya, Dagmar WilhelmAbstract:Ovarian follicular granulosa cells surround and nurture oocytes, and produce sex steroid hormones. It is believed that during development the ovarian surface epithelial cells penetrate into the ovary and develop into granulosa cells when associating with oogonia to form follicles. Using bovine fetal ovaries (n = 80) we identified a novel cell type, termed GREL for Gonadal Ridge Epithelial-Like. Using 26 markers for GREL and other cells and extracellular matrix we conducted immunohistochemistry and electron microscopy and chronologically tracked all somatic cell types during development. Before 70 days of gestation the Gonadal Ridge/ovarian primordium is formed by proliferation of GREL cells at the surface epithelium of the mesonephros. Primordial germ cells (PGCs) migrate into the ovarian primordium. After 70 days, stroma from the underlying mesonephros begins to penetrate the primordium, partitioning the developing ovary into irregularly-shaped ovigerous cords composed of GREL cells and PGCs/oogonia. Importantly we identified that the cords are always separated from the stroma by a basal lamina. Around 130 days of gestation the stroma expands laterally below the outermost layers of GREL cells forming a sub-epithelial basal lamina and establishing an epithelial-stromal interface. It is at this stage that a mature surface epithelium develops from the GREL cells on the surface of the ovary primordium. Expansion of the stroma continues to partition the ovigerous cords into smaller groups of cells eventually forming follicles containing an oogonium/oocyte surrounded by GREL cells, which become granulosa cells, all enclosed by a basal lamina. Thus in contrast to the prevailing theory, the ovarian surface epithelial cells do not penetrate into the ovary to form the granulosa cells of follicles, instead ovarian surface epithelial cells and granulosa cells have a common precursor, the GREL cell.