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https://hdl.handle.net/2440/56237
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dc.contributor.author | Chin, P. | - |
dc.contributor.author | Macpherson, A. | - |
dc.contributor.author | Thompson, J. | - |
dc.contributor.author | Lane, M. | - |
dc.contributor.author | Robertson, S. | - |
dc.date.issued | 2009 | - |
dc.identifier.citation | Human Reproduction, 2009; 24(12):2997-3009 | - |
dc.identifier.issn | 0268-1161 | - |
dc.identifier.issn | 1460-2350 | - |
dc.identifier.uri | http://hdl.handle.net/2440/56237 | - |
dc.description.abstract | BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to promote the development and survival of human and mouse preimplantation embryos; however, the mechanism of action of GM-CSF in embryos is not defined. METHODS: Mouse blastocysts were cultured from zygote stage in vitro with and without recombinant mouse GM-CSF (rmGM-CSF), and in vivo developed blastocysts were flushed from Csf2 null mutant and wild-type mice. The effect of GM-CSF on blastocyst expression of stress response and apoptosis genes was evaluated by microarray, qPCR and immunochemistry. RESULTS: Microarray analysis of the gene transcription profile showed suppression of stress response and apoptosis gene pathways in blastocysts exposed to rmGM-CSF in vitro. qPCR analysis confirmed that rmGM-CSF inhibited expression of heat shock protein (HSP) and apoptosis pathway genes Cbl, Hspa5, Hsp90aa1, Hsp90ab1 and Gas5 in in vitro blastocysts. Immunocytochemical analysis of HSP 1 (HSPA1A/1B; HSP70), BAX, BCL2 and TRP53 (p53) in in vitro blastocysts showed that HSPA1A/1B and BCL2 proteins were less abundant when embryos were cultured with rmGM-CSF. BAX and TRP53 were unchanged at the protein level, but Bax mRNA expression was reduced after GM-CSF treatment. In in vivo developed blastocysts, Csf2 null mutation caused elevated expression of Hsph1 but not other stress response genes. CONCLUSIONS: We conclude that GM-CSF inhibits the cellular stress response and apoptosis pathways to facilitate embryo growth and survival, and the protective effects of GM-CSF are particularly evident in in vitro culture media, whereas in vivo other cytokines can partly compensate for absence of GM-CSF. | - |
dc.description.statementofresponsibility | Peck Y. Chin, Anne M. Macpherson, Jeremy G. Thompson, Michelle Lane and Sarah A. Robertson | - |
dc.language.iso | en | - |
dc.publisher | Oxford Univ Press | - |
dc.source.uri | http://dx.doi.org/10.1093/humrep/dep307 | - |
dc.subject | blastocyst | - |
dc.subject | GM-CSF | - |
dc.subject | heat shock proteins | - |
dc.subject | stress response | - |
dc.subject | apoptosis | - |
dc.title | Stress response genes are suppressed in mouse preimplantation embryos by granulocyte-macrophage colony-stimulating factor (GM-CSF) | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1093/humrep/dep307 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Chin, P. [0000-0002-0923-0553] | - |
dc.identifier.orcid | Macpherson, A. [0000-0002-7674-9961] | - |
dc.identifier.orcid | Thompson, J. [0000-0003-4941-7731] | - |
dc.identifier.orcid | Robertson, S. [0000-0002-9967-0084] | - |
Appears in Collections: | Aurora harvest Obstetrics and Gynaecology publications |
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