|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
First published online 1 November 2005
doi: 10.1242/jcs.02644
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Research Article |
Research Centre for Reproductive Health, Department of Obstetrics and Gynaecology, The University of Adelaide, The Queen Elizabeth Hospital, Woodville Road, Woodville, South Australia, 5011, Australia
* Author for correspondence (e-mail: robert.gilchrist{at}adelaide.edu.au)
Accepted 15 August 2005
Paracrine factors secreted by the oocyte regulate a broad range of cumulus cell functions. Characteristically, cumulus cells have a low incidence of apoptosis and we proposed that this is due to oocyte-secreted factors acting in an anti-apoptotic manner. Bovine cumulus-oocyte complexes (COC) were aspirated from abattoir-derived ovaries and oocytectomized (OOX) by microsurgical removal of the oocyte. OOX were treated with doses of either denuded oocytes (DO) or various growth factors for 24 hours (± rFSH; 0.1 IU/ml). Proportions of apoptotic cumulus cells were assessed using TUNEL and laser confocal scanning microscopy followed by image analysis. Quantification of Bcl-2 and Bax proteins in OOX was undertaken by western analysis. Oocyte removal led to a significant increase in cumulus cell apoptosis compared with COC controls (35% versus 9% TUNEL positive, respectively; P<0.001). Levels of OOX apoptosis were significantly reversed (P<0.001) in a dose-dependent manner when co-cultured with oocytes. Furthermore, the anti-apoptotic effect of oocyte-secreted factors followed a gradient from the site of the oocyte(s). Growth differentiation factor 9 (GDF9) had no significant effect on cumulus cell apoptosis. By contrast, cumulus cell apoptosis was significantly (P<0.001) reduced by bone morphogenetic proteins (BMP) 15, 6 or 7. Accordingly, levels of anti-apoptotic Bcl-2 were high in OOX+DO and OOX+BMP15 and low with OOX+GDF9 or OOX alone, whereas the reverse was observed for pro-apoptotic Bax. DO, BMP15 and BMP6 were also able to protect cumulus cells from undergoing apoptosis induced by staurosporine. FSH partially prevented apoptosis in all treatment groups (P<0.001). Follistatin and a BMP6 neutralizing antibody, which antagonized the anti-apoptotic effects of BMP15 and BMP6, respectively, whether alone or combined, blocked 
50% of the anti-apoptotic actions of oocytes. These results are the first to demonstrate that oocyte-secreted factors, and particularly BMP15 and BMP6, maintain the low incidence of cumulus cell apoptosis by establishing a localized gradient of bone morphogenetic proteins.
Key words: Oocyte-secreted factors, Bone morphogenetic proteins, Cumulus cell, Apoptosis
This article has been cited by other articles:
|
|
 |
|
  J. E. Swain and T. B. Pool ART failure: oocyte contributions to unsuccessful fertilization Hum. Reprod. Update, September 1, 2008; 14(5): 431 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bettegowda, O. V. Patel, K.-B. Lee, K.-E. Park, M. Salem, J. Yao, J. J. Ireland, and G. W. Smith Identification of Novel Bovine Cumulus Cell Molecular Markers Predictive of Oocyte Competence: Functional and Diagnostic Implications Biol Reprod, August 1, 2008; 79(2): 301 - 309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. T. Jones Meiosis in oocytes: predisposition to aneuploidy and its increased incidence with age Hum. Reprod. Update, March 1, 2008; 14(2): 143 - 158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. B. Gilchrist, M. Lane, and J. G. Thompson Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality Hum. Reprod. Update, March 1, 2008; 14(2): 159 - 177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. X. Yeo, R. B. Gilchrist, J. G. Thompson, and M. Lane Exogenous growth differentiation factor 9 in oocyte maturation media enhances subsequent embryo development and fetal viability in mice Hum. Reprod., January 1, 2008; 23(1): 67 - 73. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-Q. Su, K. Sugiura, K. Wigglesworth, M. J. O'Brien, J. P. Affourtit, S. A. Pangas, M. M. Matzuk, and J. J. Eppig Oocyte regulation of metabolic cooperativity between mouse cumulus cells and oocytes: BMP15 and GDF9 control cholesterol biosynthesis in cumulus cells Development, January 1, 2008; 135(1): 111 - 121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J Diaz, K. Sugiura, and J. J Eppig Regulation of Pcsk6 Expression During the Preantral to Antral Follicle Transition in Mice: Opposing Roles of FSH and Oocytes Biol Reprod, January 1, 2008; 78(1): 176 - 183. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. Clelland, Q. Tan, A. Balofsky, R. Lacivita, and C. Peng Inhibition of Premature Oocyte Maturation: A Role for Bone Morphogenetic Protein 15 in Zebrafish Ovarian Follicles Endocrinology, November 1, 2007; 148(11): 5451 - 5458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sugiura, Y.-Q. Su, F. J. Diaz, S. A. Pangas, S. Sharma, K. Wigglesworth, M. J. O'Brien, M. M. Matzuk, S. Shimasaki, and J. J. Eppig Oocyte-derived BMP15 and FGFs cooperate to promote glycolysis in cumulus cells Development, July 15, 2007; 134(14): 2593 - 2603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-T. Wu, L. Tang, J. Cai, X.-E Lu, J. Xu, X.-M. Zhu, Q. Luo, and H.-F. Huang High bone morphogenetic protein-15 level in follicular fluid is associated with high quality oocyte and subsequent embryonic development Hum. Reprod., June 1, 2007; 22(6): 1526 - 1531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Dragovic, L. J. Ritter, S. J. Schulz, F. Amato, J. G. Thompson, D. T. Armstrong, and R. B. Gilchrist Oocyte-Secreted Factor Activation of SMAD 2/3 Signaling Enables Initiation of Mouse Cumulus Cell Expansion Biol Reprod, May 1, 2007; 76(5): 848 - 857. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. J. Diaz, K. Wigglesworth, and J. J. Eppig Oocytes determine cumulus cell lineage in mouse ovarian follicles J. Cell Sci., April 15, 2007; 120(8): 1330 - 1340. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Pesty, F. Miyara, P. Debey, B. Lefevre, and C. Poirot Multiparameter assessment of mouse oogenesis during follicular growth in vitro Mol. Hum. Reprod., January 1, 2007; 13(1): 3 - 9. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. B. Gilchrist, L. J. Ritter, S. Myllymaa, N. Kaivo-Oja, R. A. Dragovic, T. E. Hickey, O. Ritvos, and D. G. Mottershead Molecular basis of oocyte-paracrine signalling that promotes granulosa cell proliferation J. Cell Sci., September 15, 2006; 119(18): 3811 - 3821. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Rossi, G. Macchiarelli, M.G. Palmerini, R. Canipari, and S. Cecconi Meiotic spindle configuration is differentially influenced by FSH and epidermal growth factor during in vitro maturation of mouse oocytes Hum. Reprod., July 1, 2006; 21(7): 1765 - 1770. [Abstract] [Full Text] [PDF]
|
|
