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Type: Journal article
Title: Granulocyte-macrophage colony-stimulating factor (GM-CSF) acts independently of the beta common subunit of the GM-CSF receptor to prevent inner cell mass apoptosis in human embryos
Author: Sjoblom, C.
Wikland, M.
Robertson, S.
Citation: Biology of Reproduction, 2002; 67(6):1817-1823
Publisher: Soc Study Reproduction
Issue Date: 2002
ISSN: 0006-3363
Statement of
Cecilia Sjöblom, Matts Wikland, and Sarah A. Robertson
Abstract: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is expressed in the female reproductive tract during early pregnancy and can promote the growth and development of preimplantation embryos in several species. We have demonstrated with in vitro experiments that the incidence of blastulation in human embryos is increased approximately twofold when GM-CSF is present in the culture medium. In the present study, we investigated the mechanisms underlying the embryotrophic actions of GM-CSF. Using reverse transcription-polymerase chain reaction and immunocytochemistry, expression of mRNA and protein of the GM-CSF-receptor alpha subunit (GM-R) was detected in embryos from the first-cleavage through blastocyst stages of development, but the GM-CSF-receptor beta common subunit (ßc) could not be detected at any stage. When neutralizing antibodies reactive with GM-R were added to embryo culture experiments, the development-promoting effect of GM-CSF was ablated. In contrast, GM-CSF activity in embryos was not inhibited either by antibodies to ßc or by E21R, a synthetic GM-CSF analogue that acts to antagonize ßc-mediated GM-CSF signaling. Unexpectedly, E21R was found to mimic native GM-CSF in promoting blastulation. When embryos were assessed for apoptosis and cell number by confocal microscopy after TUNEL and propidium iodine staining, it was found that blastocysts cultured in GM-CSF contained 50% fewer apoptotic nuclei and 30% more viable inner cell mass cells. Together, these data indicate that GM-CSF regulates cell viability in human embryos and that this potentially occurs through a novel receptor mechanism that is independent of ßc.
Keywords: Blastocyst
Granulocyte-Macrophage Colony-Stimulating Factor
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
Recombinant Proteins
RNA, Messenger
Culture Media
Microscopy, Confocal
Culture Techniques
In Situ Nick-End Labeling
Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Gene Expression
Embryonic Development
Embryo, Mammalian
Description: © 2002 Society for the Study of Reproduction, Inc.
DOI: 10.1095/biolreprod.101.001503
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Appears in Collections:Aurora harvest 4
Obstetrics and Gynaecology publications

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