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https://hdl.handle.net/2440/17288
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Type: | Journal article |
Title: | Oocytes prevent cumulus cell apoptosis by maintaining a morphogenic paracrine gradient of bone morphogenetic proteins |
Author: | Hussein, T. Froiland, D. Amato, F. Thompson, J. Gilchrist, R. |
Citation: | Journal of Cell Science, 2005; 118(22):5257-5268 |
Publisher: | Company of Biologists Ltd |
Issue Date: | 2005 |
ISSN: | 0021-9533 1477-9137 |
Statement of Responsibility: | Tamer S. Hussein, David A. Froiland, Fred Amato, Jeremy G. Thompson and Robert B. |
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. |
Keywords: | oocyte-secreted factors bone morphogenetic proteins cumulus cell apoptosis |
Description: | © The Company of Biologists Ltd 2005 |
DOI: | 10.1242/jcs.02644 |
Published version: | http://jcs.biologists.org/cgi/content/abstract/118/22/5257 |
Appears in Collections: | Aurora harvest 6 Obstetrics and Gynaecology publications |
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