Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/17288
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dc.contributor.author | Hussein, T. | - |
dc.contributor.author | Froiland, D. | - |
dc.contributor.author | Amato, F. | - |
dc.contributor.author | Thompson, J. | - |
dc.contributor.author | Gilchrist, R. | - |
dc.date.issued | 2005 | - |
dc.identifier.citation | Journal of Cell Science, 2005; 118(22):5257-5268 | - |
dc.identifier.issn | 0021-9533 | - |
dc.identifier.issn | 1477-9137 | - |
dc.identifier.uri | http://hdl.handle.net/2440/17288 | - |
dc.description | © The Company of Biologists Ltd 2005 | - |
dc.description.abstract | 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 antiapoptotic 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. | - |
dc.description.statementofresponsibility | Tamer S. Hussein, David A. Froiland, Fred Amato, Jeremy G. Thompson and Robert B. | - |
dc.language.iso | en | - |
dc.publisher | Company of Biologists Ltd | - |
dc.source.uri | http://jcs.biologists.org/cgi/content/abstract/118/22/5257 | - |
dc.subject | oocyte-secreted factors | - |
dc.subject | bone morphogenetic proteins | - |
dc.subject | cumulus cell | - |
dc.subject | apoptosis | - |
dc.title | Oocytes prevent cumulus cell apoptosis by maintaining a morphogenic paracrine gradient of bone morphogenetic proteins | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1242/jcs.02644 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Thompson, J. [0000-0003-4941-7731] | - |
dc.identifier.orcid | Gilchrist, R. [0000-0003-1611-7142] | - |
Appears in Collections: | Aurora harvest 6 Obstetrics and Gynaecology publications |
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hdl_17288.pdf | 636.5 kB | Publisher's PDF | View/Open |
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