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https://hdl.handle.net/2440/56237
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Type: | Journal article |
Title: | Stress response genes are suppressed in mouse preimplantation embryos by granulocyte-macrophage colony-stimulating factor (GM-CSF) |
Author: | Chin, P. Macpherson, A. Thompson, J. Lane, M. Robertson, S. |
Citation: | Human Reproduction, 2009; 24(12):2997-3009 |
Publisher: | Oxford Univ Press |
Issue Date: | 2009 |
ISSN: | 0268-1161 1460-2350 |
Statement of Responsibility: | Peck Y. Chin, Anne M. Macpherson, Jeremy G. Thompson, Michelle Lane and Sarah A. Robertson |
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. |
Keywords: | blastocyst GM-CSF heat shock proteins stress response apoptosis |
DOI: | 10.1093/humrep/dep307 |
Published version: | http://dx.doi.org/10.1093/humrep/dep307 |
Appears in Collections: | Aurora harvest Obstetrics and Gynaecology publications |
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