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Masayuki Shimada - One of the best experts on this subject based on the ideXlab platform.
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inductions of granulosa cell luteinization and Cumulus expansion are dependent on the fibronectin integrin pathway during ovulation process in mice
PLOS ONE, 2018Co-Authors: Hiroya Kitasaka, Tomoko Kawai, S Masudul A Hoque, Takashi Umehara, Youko Fujita, Masayuki ShimadaAbstract:It has been known that EGF-like factor secreted from LH-stimulated granuloma cells acts on granulosa cells and Cumulus cells to induce ovulation process. Granulosa cells are changed the morphology with differentiating cell functions to produce progesterone. Cumulus cells are detached to make a space between the cells to accumulate hyaluronan rich matrix. LH also changes extracellular matrix (ECM) components including fibronectin in the follicular walls and granulosa cell layers. EGF like factor and fibronectin synergistically play important roles in numerous cell functions, especially cancer cell migration, estimating that fibronectin would impact on granulosa cells and Cumulus cells. To clear this hypothesis, the localizations of fibronectin and its receptor integrin were observed by immunofluorescence technique. The functions were monitored by the detection of downstream signaling pathway, focal adhesion kinase (FAK). The pharmacological approach in both in vivo and in vitro were used for analyzing the physiological roles of FAK during ovulation process. The immunofluorescence staining revealed that fibronectin and integrin were observed in granulosa cells, Cumulus cells and the space between Cumulus cells and oocyte at 4 and 8 h after hCG injection. Concomitantly with the changes of fibronectin-integrin localization, FAK was phosphorylated in periovulatory follicles. The injection of FAK inhibitor suppressed not only ovulation but also luteinization of granulosa cells and Cumulus expansion. In cultured-granulosa cells, fibronectin-integrin synergistically activated FAK with amphiregulin (AREG). Such cooperative stimulations induced a morphological change in granulosa cells, which resulted in the maximum level of progesterone production via the induction of Hsd3b. When Cumulus-oocyte complexes (COCs) were cultured with AREG in the presence of serum, the maximum level of Cumulus expansion was observed. The AREG-induced Cumulus expansion was also suppressed by FAK inhibitor. Thus, it is concluded that fibronectin and AREG synergistically activate FAK not only in granulosa cells and Cumulus cells to induce successful ovulation process.
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Regulation of oocyte meiotic maturation by somatic cells
Reproductive Medicine and Biology, 2012Co-Authors: Masayuki ShimadaAbstract:In preovulatory follicles, each oocyte is surrounded by numerous layers of Cumulus cells, forming the Cumulus cell–oocyte complex. An LH surge induces meiotic resumption of the oocyte to progress to metaphase II. Because the expression of LH receptors is not detected in the oocyte and is minimal (negligible) in Cumulus cells as compared with granulosa cells, secondary factors from granulosa cells are required to induce the ovulation process. One of the key factors secreted from granulosa cells is an EGF-like factor that activates the EGFR–ERK1/2 pathway in Cumulus cells. The activated ERK1/2 pathway is not only involved in gene expression but also essential for the close of gap-junctional communication among Cumulus cells and between Cumulus cells and the oocyte. Closing gap-junctional communication decreases the amount of cGMP and/or cAMP to transfer into the oocyte, which requires activation of phosphodiesterase type III (PDE3) in the oocyte. PDE3 brakes down cAMP to decrease PKA activity in the oocyte. This decrease in PKA activity induces activation of CDK1 to resume meiosis from the germinal vesicle stage. Thus, the functions of Cumulus cells that are regulated by granulosa cell-secreted factors are essential for oocyte meiotic resumption and maturation with developmental competence.
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The Role of Cumulus Cells in Fertilization Process
Journal of Fertilization: In vitro, 2012Co-Authors: Masayuki ShimadaAbstract:Copyright: © 2012 Shimada M. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. During ovulation process, Cumulus cells produced and accumulated hyaluronan (HA) rich matrix within Cumulus cell layers, called as Cumulus expansion. The expanded Cumulus oocyte complex is ovulated from follicle, and then fertilized in oviduct. It has been known that the fertilization rate of oocyte in vitro is higher when expanded COCs are used for in vitro fertilization as compared with that in denuded oocyte. However, the positive roles of Cumulus cells in fertilization process were remained unclear.
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Activation of PKA, p38 MAPK and ERK1/2 by gonadotropins in Cumulus cells is critical for induction of EGF-like factor and TACE/ADAM17 gene expression during in vitro maturation of porcine COCs
Journal of Ovarian Research, 2009Co-Authors: Yasuhisa Yamashita, Mitsugu Hishinuma, Masayuki ShimadaAbstract:Objectives During ovulation, it has been shown that LH stimulus induces the expression of numerous genes via PKA, p38 MAPK, PI3K and ERK1/2 in Cumulus cells and granulosa cells. Our recent study showed that EGF-like factor and its protease (TACE/ADAM17) are required for the activation of EGF receptor (EGFR), Cumulus expansion and oocyte maturation of porcine Cumulus-oocyte complexes (COCs). In the present study, we investigated which signaling pathways are involved in the gene expression of EGF-like factor and in Tace/Adam17 expression in Cumulus cells of porcine COC during in vitro maturation. Methods Areg , Ereg , Tace/Adam17 , Has2 , Tnfaip6 and Ptgs2 mRNA expressions were detected in Cumulus cells of porcine COCs by RT-PCR. Protein level of ERK1/2 phosphorylation in cultured Cumulus cells was analyzed by westernblotting. COCs were visualized using a phase-contrast microscope. Results When COCs were cultured with FSH and LH up to 2.5 h, Areg , Ereg and Tace/Adam17 mRNA were expressed in Cumulus cells of COCs. Areg , Ereg and Tace/Adam17 gene expressions were not suppressed by PI3K inhibitor (LY294002), whereas PKA inhibitor (H89), p38 MAPK inhibitor (SB203580) and MEK inhibitor (U0126) significantly suppressed these gene expressions. Phosphorylation of ERK1/2, and the gene expression of Has2 , Tnfaip6 and Ptgs2 were also suppressed by H89, SB203580 and U0126, however, these negative effects were overcome by the addition of EGF to the medium, but not in the U0126 treatment group. Conclusion The results showed that PKA, p38 MAPK and ERK1/2 positively controlled the expression of EGF-like factor and TACE/ADMA17, the latter of which impacts the Cumulus expansion and oocyte maturation of porcine COCs via the EGFR-ERK1/2 pathway in Cumulus cells.
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Cumulus Oocyte Complex: Cumulus Cells Regulate Oocyte Growth and Maturation
Journal of Mammalian Ova Research, 2009Co-Authors: Masayuki ShimadaAbstract:Abstract: Cumulus cells directly surround oocyte to form Cumulus oocyte complex (COC). Oocyte secreted factors act on Cumulus cells to regulate the specific functions. Since oocytes have less glycolytic activity, the energy sources, such as piruvate or amino acid, are transferred from Cumulus cells to oocyte via gap junctional communications, which are required for oocyte growth. After the LH surge, granulosa cells produce EGF-like factors that act on Cumulus cells to induce Cumulus expansion and oocyte maturation. EGF receptor expressed on Cumulus cells up-regulates the ERK1/2-dependent pathway. The signaling pathway plays important roles in oocyte meiotic maturation and Cumulus expansion (accumulation of hyaluronan-rich matrix within Cumulus cell layers). During the fertilization process, the hyaluronan-rich matrix is broken down and the small hyaluronan fragments stimulate Cumulus cells via the toll-like receptor (TLR) pathway to secrete the chemokine family. The secret chemokines act on sperm to induc...
Darryl L. Russell - One of the best experts on this subject based on the ideXlab platform.
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Molecular Filtration Properties of the Mouse Expanded Cumulus Matrix: Controlled Supply of Metabolites and Extracellular Signals to Cumulus Cells and the Oocyte
Biology of Reproduction, 2012Co-Authors: Kylie R. Dunning, Rebecca L. Robker, Laura N. Watson, Jeremy G. Thompson, David J. Sharkey, Hannah M. Brown, Robert J. Norman, Darryl L. RussellAbstract:While formation of the expanded Cumulus matrix and its importance for oocyte maturation and ovulation are well described, its function in these processes remains unknown. The degree of expansion and expression of Cumulus matrix genes are positively correlated with oocyte quality, suggesting that this matrix plays a key role in oocyte maturation. Based on recognized filtration properties of analogous matrices, we investigated whether the Cumulus matrix acts as a molecular filter by assessing diffusion of fluorescently labeled dextrans (neutral and negatively charged) and hydrophilic (glucose) and hydrophobic (cholesterol) metabolites in Cumulus oocyte complexes (COCs). Expanded in vivo-matured COCs resisted absorption of glucose and cholesterol compared to unexpanded COCs. In vitro-matured (IVM) COCs have a pronounced deficiency in Cumulus matrix proteins and have poor oocyte quality. Here we demonstrate that IVM Cumulus matrix has deficient filtration properties, with dextran and glucose and cholesterol molecules diffusing more readily into IVM than in vivo-matured COCs. Taking the inverse approach, we found that prostaglandin E2 (PGE2), synthesized by Cumulus cells, is retained within the matrix of in vivo-matured COCs but IVM COCs have reduced capacity to retain PGE2, secreting significantly more into the medium. This is the first demonstration of a biophysical property of the Cumulus matrix. The ability to regulate metabolite supply from the surrounding environment while sequestering vital signaling factors, such as PGE2, is likely to impact oocyte maturation. Thus, IVM may reduce oocyte quality due to dysregulated control of metabolites and signaling molecules.
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human Cumulus cell gene expression as a biomarker of pregnancy outcome after single embryo transfer
Fertility and Sterility, 2011Co-Authors: Kathryn Gebhardt, Kylie R. Dunning, Deanne Feil, Michelle Lane, Darryl L. RussellAbstract:Objective To identify the Cumulus cell gene expression associated with oocyte developmental competence, specifically live birth, after single ET (SET) assisted reproductive technology. Design Retrospective gene expression analysis in human Cumulus cells from oocytes that established a pregnancy resulting in live birth versus no pregnancy after SET. Setting Independent IVF clinic and research institute. Patient(s) Women undergoing IVF/intracytoplasmic sperm injection with SET. Intervention(s) Quantitative reverse-transcriptase–polymerase chain reaction analysis was performed on Cumulus masses collected before insemination. Oocytes and embryos were cultured and transferred independently in 38 patients undergoing elective SET. Paired Cumulus samples from oocytes that developed into high- versus low-grade embryos also were compared. Main Outcome Measure(s) Gene expression profiles of metabolic ( ALDOA, LDHA, PFKP, PKM2 ), signaling ( AHR, GREM1, PTGS2, STS ), extracellular matrix ( HAS2, PTX3, TNFAIP6, VCAN ), and loading control GAPDH in individual Cumulus masses. Result(s) VCAN and PTGS2 mRNA expression was significantly higher in Cumulus cells from oocytes yielding a pregnancy resulting in a live birth, while PTX3 mRNA expression trended toward higher expression in pregnant samples. Cumulus cell levels of VCAN , GREM1 , and PFKP correlated with birth weight in patients at 38 weeks of gestation. No genes correlated with clinical embryo morphology scores. Conclusion(s) Cumulus cell VCAN , PTGS2, GREM1 , and PFKP expression may identify oocytes with high developmental potential, leading to enhanced implantation rates and greater developmental capacity throughout gestation.
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146. MOLECULAR FILTRATION PROPERTIES OF THE EXPANDED Cumulus MATRIX: CONTROLLED SUPPLY OF METABOLITES AND EXTRACELLULAR SIGNALS TO Cumulus CELLS AND THE OOCYTE
Reproduction Fertility and Development, 2010Co-Authors: Kylie R. Dunning, Rebecca L. Robker, Laura N. Watson, Jeremy G. Thompson, Darryl L. RussellAbstract:Cumulus matrix genes are positively correlated with oocyte competence [1]. Formation of the expanded Cumulus matrix during oocyte maturation is well described; however its function remains elusive. We investigated whether Cumulus matrix acts as a molecular filter, based on recognised filtration properties of analogous matrices. We found that Cumulus matrix controls metabolite supply to the oocyte and retains prostaglandin E2 (PGE2), which is critical in oocyte maturation. The uptake of fluorescently labelled hydrophilic and hydrophobic metabolites showed that Cumulus matrix formation significantly impeded diffusion to the oocyte. Expanded in vivo matured Cumulus oocyte complexes (COCs, eCG+hCG16h) resisted uptake of glucose and cholesterol compared to unexpanded (eCG44h, P < 0.05), as assessed by confocal microscopy and spatial quantitation of fluorescence (P < 0.05). In vitro maturation (IVM) results in pronounced compositional deficiency of Cumulus matrix proteins [2] and poor oocyte quality. Glucose and cholesterol were transported more readily into Cumulus cells and the oocyte of IVM COCs (matured in αMEM/5% FCS/50 mIU/mL FSH, 16 h) compared to in vivo matured COCs (P < 0.05 and P = 0.08, respectively). Taking the inverse approach we found that PGE2 synthesised by Cumulus cells is retained within the matrix compartment of in vivo matured COCs but IVM COCs did not retain PGE2 and secreted 4.3-fold more into the media. The relationship of retained to secreted PGE2 was significantly higher after in vivo maturation vs IVM COCs (P < 0.0001). This property of the COC matrix reveals a potential mechanism whereby the prostaglandin signal intensifies through a physicochemical mechanism rather than gene regulation. This is the first demonstration that Cumulus matrix regulates diffusion toward and secretion from the COC, thus excluding glucose, known to negatively affect oocyte quality, and trapping factors, including PGE2, with critical roles in oocyte maturation and fertilisation. Thus, IVM may reduce oocyte quality due to poor trafficking of metabolites and signalling molecules. (1) McKenzie LJ, et al. Human Cumulus granulosa cell gene expression: a predictor of fertilization and embryo selection in women undergoing IVF. Hum Reprod 2004; 19: 2869–2874. (2) Dunning KR, et al. Altered composition of the Cumulus-oocyte complex matrix during in vitro maturation of oocytes. Hum Reprod 2007; 22: 2842–2850.
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155. CD44 SIGNALLING IN THE Cumulus OOCYTE COMPLEX DURING OVULATION
Reproduction Fertility and Development, 2009Co-Authors: Emily R. Alvino, Rebecca L. Robker, Darryl L. RussellAbstract:Oocytes develop within ovarian follicles that nurture and regulate oocyte maturation. The LH surge induces a cascade of gene expression leading to formation of the hyaluronan (HA) rich Cumulus matrix around the oocyte. This Cumulus oocyte complex (COC) is composed of high concentrations of HA cross-linked by several HA-binding proteins. Null mutation of several COC matrix genes results in ovulation defects demonstrating the importance of the composition and structure of the COC; but the mechanisms by which the matrix promotes ovulation are unknown. We hypothesised that HA, via activation of its receptor CD44 on Cumulus cells, regulates cytoskeletal function, cell adhesion and migration, and that acquired Cumulus cell motility facilitates ovulation. We investigated cellular signaling and cellular phenotypes occurring in response to the formation of the HA-rich COC matrix. Expression of CD44 was upregulated 5 to 6-fold in Cumulus cells following 6 or 12h hCG (LH analog) stimulation. Signal transducers of CD44 action; Tiam1, a guanine exchange factor, and Rac1, an actin cytoskeleton remodelling Rho-family GTPase, were present in Cumulus cells but not regulated by hCG. Induction of migratory and invasive capacity of Cumulus cells by hCG was demonstrated using transwell migration and ECM invasion assays. Cumulus cell migration increased 8-fold 10h after hCG compared with Cumulus cells from untreated mice. These Cumulus cells also showed the capacity to invade through a matrigel barrier. Inhibitors of the CD44-assembled cell migration complex demonstrated the importance of this pathway in the migratory and invasive phenotype of Cumulus cells. These results demonstrate that CD44 is a key factor in the assembly of a macromolecular complex facillitating cell motility in Cumulus cells at the time of ovulation, and suggest that Cumulus cells in the expanded COC undergo epithelial-mesenchymal transition to become invasive motile cells which may play a key role mediating ovulation.
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Extracellular matrix of the Cumulus-oocyte complex.
Seminars in Reproductive Medicine, 2006Co-Authors: Darryl L. Russell, Antonietta SalustriAbstract:The mammalian oocyte is surrounded by several layers of Cumulus granulosa cells that nurture the oocyte during its development and actively participate in the process of ovulation. After the ovulatory luteinizing hormone surge, a distinctive program of extracellular matrix production is initiated in the Cumulus-oocyte complex. This process known as Cumulus expansion or mucification involves synthesis of a backbone of long hyaluronan oligosaccharide chains that are cross-linked by a complex of hyaluronan binding cell surface and extracellular matrix proteins and proteoglycans. Active components of the Cumulus matrix are synthesized directly by Cumulus cells under the control of endocrine- and oocyte-derived factors, secreted by mural granulosa cells, or enter the follicle in blood plasma. Appropriate composition and assembly of the Cumulus matrix is essential for ovulation, efficient passage of the oocyte through the oviduct, and for fertilization. This review describes the critical components and their functional roles in the Cumulus matrix, as well as the molecular regulation of Cumulus matrix gene expression.
Martin M Matzuk - One of the best experts on this subject based on the ideXlab platform.
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Oocyte regulation of metabolic cooperativity between mouse Cumulus cells and oocytes: BMP15 and GDF9 control cholesterol biosynthesis in Cumulus cells.
Development, 2007Co-Authors: Koji Sugiura, Stephanie A Pangas, Martin M Matzuk, Karen Wigglesworth, Marilyn J. O'brien, Jason P. Affourtit, John J. EppigAbstract:Oocyte-derived bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) are key regulators of follicular development. Here we show that these factors control Cumulus cell metabolism, particularly glycolysis and cholesterol biosynthesis before the preovulatory surge of luteinizing hormone. Transcripts encoding enzymes for cholesterol biosynthesis were downregulated in both Bmp15 -/- and Bmp15 -/- Gdf9 +/- double mutant Cumulus cells, and in wild-type Cumulus cells after removal of oocytes from Cumulus-cell-oocyte complexes. Similarly, cholesterol synthesized de novo was reduced in these Cumulus cells. This indicates that oocytes regulate Cumulus cell cholesterol biosynthesis by promoting the expression of relevant transcripts. Furthermore, in wild-type mice, Mvk, Pmvk, Fdps, Sqle, Cyp51, Sc4mol and Ebp, which encode enzymes required for cholesterol synthesis, were highly expressed in Cumulus cells compared with oocytes; and oocytes, in the absence of the surrounding Cumulus cells, synthesized barely detectable levels of cholesterol. Furthermore, coincident with reduced cholesterol synthesis in double mutant Cumulus cells, lower levels were also detected in Cumulus-cell-enclosed double mutant oocytes compared with wild-type oocytes. Levels of cholesterol synthesis in double mutant Cumulus cells and oocytes were partially restored by co-culturing with wild-type oocytes. Together, these results indicate that mouse oocytes are deficient in synthesizing cholesterol and require Cumulus cells to provide products of the cholesterol biosynthetic pathway. Therefore, oocyte-derived paracrine factors, particularly, BMP15 and GDF9, promote cholesterol biosynthesis in Cumulus cells, probably as compensation for oocyte deficiencies in cholesterol production.
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oocyte derived bmp15 and fgfs cooperate to promote glycolysis in Cumulus cells
Development, 2007Co-Authors: Koji Sugiura, Stephanie A Pangas, Martin M Matzuk, Karen Wigglesworth, Francisco Javier Diaz, Marilyn J Obrien, Shweta Sharma, Shunichi Shimasaki, John J. EppigAbstract:Mammalian oocytes are deficient in their ability to carry out glycolysis. Therefore, the products of glycolysis that are necessary for oocyte development are provided to oocytes by companion Cumulus cells. Mouse oocytes secrete paracrine factors that promote glycolysis in Cumulus cells. The objective of this study was to identify paracrine factors secreted by oocytes that promote glycolysis and expression of mRNA encoding the glycolytic enzymes PFKP and LDHA. Candidates included growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15) and fibroblast growth factors (FGFs). Bmp15-/- and Gdf9+/- Bmp15-/- (double mutant, DM) Cumulus cells exhibited reduced levels of both glycolysis and Pfkp and Ldha mRNA, and mutant oocytes were deficient in promoting glycolysis and expression of Pfkp and Ldha mRNA in Cumulus cells of wild-type (WT) mice. Alone, neither recombinant BMP15, GDF9 nor FGF8 promoted glycolysis and expression of Pfkp and Ldha mRNA in WT Cumulus cells. Co-treatment with BMP15 and FGF8 promoted glycolysis and increased expression of Pfkp and Ldha mRNA in WT Cumulus cells to the same levels as WT oocytes; however, the combinations of BMP15/GDF9 or GDF9/FGF8 did not. Furthermore, SU5402, an FGF receptor-dependent protein kinase inhibitor, inhibited Pfkp and Ldha expression in Cumulus cells promoted by paracrine oocyte factors. Therefore, oocyte-derived BMP15 and FGFs cooperate to promote glycolysis in Cumulus cells.
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human Cumulus granulosa cell gene expression a predictor of fertilization and embryo selection in women undergoing ivf
Human Reproduction, 2004Co-Authors: Laurie J. Mckenzie, Pauline Cisneros, Sandra A Carson, Ertug Kovanci, Paula Amato, John E. Buster, Stephanie A Pangas, Martin M MatzukAbstract:BACKGROUND: A biochemical marker for embryo development would increase the chance of a successful pregnancy with IVF by optimizing oocyte and embryo selection, and allow fewer embryos to be transferred. In this study, we correlated Cumulus granulosa cell gene expression of hyaluronic acid synthase 2 (HAS2), cyclooxygenase 2( COX2; PTGS2) and gremlin (GREM1) with subsequent embryo development in search of a parameter for embryo selection. METHODS: Cumulus cell gene expression was determined prospectively on eight consecutive patients undergoing IVF with ICSI. Immediately following oocyte retrieval, the Cumulus was stripped from the oocyte, and Cumulus gene expression for PTGS2, HAS2 and GREM1 was assessed using a one-step real-time quantitative RT –PCR assay. Oocyte quality, fertilization and embryo morphology were correlated to relative gene expression. RESULTS: Gene expression data were available on Cumulus cells from 108 oocytes that developed into 70 embryos (64.8% fertilization rate). Cumulus PTGS2, HAS2 and GREM1 expression was higher from oocytes that developed into higher quality embryos (grades 3, 4 and 5) compared with lower quality embryos (grades 1 and 2) ( P< 0.05, P< 0.001 and P< 0.001, respectively). HAS2 and GREM1 expression was also higher from the Cumulus surrounding oocytes that gave rise to higher grade embryos ( P< 0.001). The expression of PTGS2 and HAS2 was 6-fold higher, and that of GREM1 was 15-fold higher in Cumulus yielding higher grade embryos versus lower grade embryos. CONCLUSION: PTGS2, HAS2 and GREM1 gene expression correlates to morphological and physiological characteristics and provides a novel approach to predict human embryo development. Ultimately, with better predictors of follicular and embryonic health, higher quality embryos can be selected and transferred, reducing higher order pregnancy rates.
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synergistic roles of bmp15 and gdf9 in the development and function of the oocyte Cumulus cell complex in mice genetic evidence for an oocyte granulosa cell regulatory loop
Developmental Biology, 2004Co-Authors: Marilyn J Obrien, Martin M Matzuk, Frank L Pendola, James N Denegre, John J. EppigAbstract:Bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) are oocyte-specific growth factors that appear to play key roles in granulosa cell development and fertility in most mammalian species. We have evaluated the role(s) of these paracrine factors in the development and function of both the Cumulus cells and oocytes by assessing Cumulus expansion, oocyte maturation, fertilization, and preimplantation embryogenesis in Gdf9+/-Bmp15-/- [hereafter, double mutant (DM)] mice. We found that Cumulus expansion, as well as the expression of hyaluronon synthase 2 (Has2) mRNA was impaired in DM oocyte-Cumulus cell complexes. This aberrant Cumulus expansion was not remedied by coculture with normal wild-type (WT) oocytes, indicating that the development and/or differentiation of Cumulus cells in the DM, up to the stage of the preovulatory luteinizing hormone (LH) surge, is impaired. In addition, DM oocytes failed to enable FSH to induce Cumulus expansion in WT oocytectomized (OOX) Cumulus. Moreover, LH-induced oocyte meiotic resumption was significantly delayed in vivo, and this delayed resumption of meiosis was correlated with the reduced activation of mitogen-activated protein kinase (MAPK) in the Cumulus cells, thus suggesting that GDF9 and BMP15 also regulate the function of Cumulus cells after the preovulatory LH surge. Although spontaneous in vitro oocyte maturation occurred normally, oocyte fertilization and preimplantation embryogenesis were significantly altered in the DM, suggesting that the full complement of both GDF9 and BMP15 are essential for the development and function of oocytes. Because receptors for GDF9 and BMP15 have not yet been identified in mouse oocytes, the effects of the mutations in the Bmp15 and Gdf9 genes on oocyte development and functions must be produced indirectly by first affecting the granulosa cells and then the oocyte. Therefore, this study provides further evidence for the existence and functioning of an oocyte-granulosa cell regulatory loop.
John Michael Bedford - One of the best experts on this subject based on the ideXlab platform.
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spermatozoa of the shrew suncus murinus undergo the acrosome reaction and then selectively kill cells in penetrating the Cumulus oophorus
Biology of Reproduction, 2001Co-Authors: Takane Kaneko, Hiroshi Iida, John Michael BedfordAbstract:In the musk shrew, Suncus murinus (and other shrews), the Cumulus oophorus is ovulated as a discrete, compact, matrix-free ball of cells linked by specialized junctions. In examining how they penetrate the Cumulus, Suncus spermatozoa were observed to first bind consistently by the ventral face over the acrosomal region to the exposed smooth surface of a peripheral Cumulus cell. This was apparently followed by point fusions between the plasma and outer acrosomal membranes. Thereafter, spermatozoa without acrosomes were observed within Cumulus cells that displayed signs of necrosis, as did some radially neighboring Cumulus cells linked by zona adherens and gap junctions. Eventually, penetration of spermatozoa as far as the perizonal space around the zona pellucida left linear tracks of locally necrotic cells flanked by normal Cumulus cells. Based on these and previous observations, we conclude that the acrosome reaction in Suncus is always induced by Cumulus cells, and that reacted spermatozoa penetrate the Cumulus by selective invasion and killing of Cumulus cells along a linear track. Loss of the acrosome also exposes an apical body/perforatorium that is covered with barbs that appear to assist reacted fertilizing spermatozoa in binding to the zona pellucida. Because fertilized eggs displayed no other spermatozoa within or bound to the zona, an efficient block to polyspermy must prevent such binding of additional spermatozoa.
T A E Stout - One of the best experts on this subject based on the ideXlab platform.
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protective effects of the Cumulus corona radiata complex during vitrification of horse oocytes
Reproduction, 2009Co-Authors: T Tharasanit, S Colleoni, Cesare Galli, B Colenbrander, T A E StoutAbstract:Vitrifying oocytes is a potentially valuable means of preserving the female germ line, but significantly compromises oocyte developmental competence. This study examined the hypothesis that the Cumulus complex protects the oocyte during vitrification. Vitrified-warmed immature Cumulus oocyte complexes (COCs) were labelled with a plasma membrane impermeant DNA marker (ethidium homodimer-1) to examine the percentage and location of dead Cumulus cells, and to investigate the effect of the proportion of dead cells (+1,+2 or +3) on the success of in vitro maturation (IVM). Further, oocytes were labelled for connexin-43 or injected with Lucifer yellow dye to determine whether the integrity of the gap junctions between an oocyte and its Cumulus was compromised by vitrification. Finally, the effect of denuding immature and mature oocytes on their ability to withstand vitrification was examined. Cryopreserving immature COCs increased the number of dead Cumulus cells (13 vs 2.6% for controls; P<0.05). However, an increased proportion of dead Cumulus cells did not affect post-warming maturation rates (approximately 30% MII) presumably because dead cells were located at the periphery of the Cumulus mass and Cumulus-oocyte gap junction communication was not disrupted. Moreover, Cumulus removal prior to IVM or vitrification indicated that while the Cumulus does protect immature oocytes during vitrification it does so by mechanisms other than support during maturation. Cumulus presence was also found to protect mature equine oocytes against vitrification-induced damage since Cumulus-enclosed MII oocytes preserved their meiotic spindle quality better during vitrification than denuded oocytes (38.1 vs 3.1% normal spindles; P<0.05).
