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BOR - Papers in Press, published online ahead of print May 5, 2004.
Biol Reprod 2004, 10.1095/biolreprod.103.026963
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BIOLOGY OF REPRODUCTION 71, 871–877 (2004)
DOI: 10.1095/biolreprod.103.026963
© 2004 by the Society for the Study of Reproduction, Inc.

Embryo

TRAIL and KILLER Are Expressed and Induce Apoptosis in the Murine Preimplantation Embryo1

Joan K. Riley3, Jennifer M. Heeley3, Amanda H. Wyman3, Elizabeth L. Schlichting3, and Kelle H. Moley2,3,4

Department of Obstetrics and Gynecology3 Department of Cell Biology and Physiology,4 Washington University School of Medicine, St. Louis, Missouri 63110

TRAIL (tumor necrosis factor [TNF]-related apoptosis-inducing ligand) and KILLER are a death-inducing ligand and receptor pair that belong to the TNF and TNF-receptor superfamilies, respectively. To date, only one apoptosis-inducing TRAIL receptor (murine KILLER [MK]) has been identified in mice, and it is a homologue of human Death Receptor 5. Whereas the expression of other death receptors, such as Fas and TNF receptor 1 have been documented in mammalian preimplantation embryos, no evidence currently demonstrates either the presence or the function of TRAIL and its corresponding death receptor, MK. Using reverse transcription-polymerase chain reaction and confocal immunofluorescent microscopy, we found that both TRAIL and MK are expressed from the 1-cell through the blastocyst stage of murine preimplantation embryo development. These proteins are localized mainly at the cell surface from the 1-cell through the morula stage. At the blastocyst stage, both TRAIL and MK exhibit an apical staining pattern in the trophectoderm cells. Finally, using the TUNEL assay, we demonstrated that MK induces apoptosis in blastocysts sensitized to TRAIL via actinomycin D. Taken together, these data are the first to demonstrate the presence and function of TRAIL and MK, a death-inducing ligand and its receptor, in mammalian preimplantation embryos.

1 Supported by a Lalor Foundation Fellowship to J.K.R. and by HD38061-01 from the National Institutes of Health to K.H.M.

2 Correspondence: Kelle H. Moley, 4911 Barnes-Jewish Hospital Plaza, St. Louis, MO 63110. FAX: 314 747 4150; moleyk{at}msnotes.wustl.edu




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