title: Survivin acts as an antiapoptotic factor during the development of mouse preimplantation embryos.
abstract: Apoptosis is an essential physiologic process used in almost all tissues to remove damaged or superfluous cells. However, the early embryos are unique because no cell death is found up to the blastocyst stage during normal development. Survivin, a member of the IAP family, is capable of binding to caspases to modulate their functions. Here, we investigated the expression of survivin, and its role in preventing apoptosis in mouse preimplantation embryos. Transcripts for survivin and a splice variant lacking exon 2 were detected from unfertilized oocytes up to hatched blastocyst stage. At the protein level, survivin was also detected at all stages of early embryos. The antisense approach was used to demonstrate the role of survivin on embryo development. Development of early embryos treated with antisense survivin oligonucleotides was arrested at the morula or early blastocyst stage with disruption of tubulin formation and abnormal nuclei, associated with apoptosis. The effect of the antisense was enhanced by cotreatment with an apoptosis-inducing reagent, staurosporine. In contrast, apoptosis induced by the antisense treatment was inhibited by caspase-3 and -9 inhibitors. These results indicate that survivin is an essential antiapoptotic gene expressed in preimplantation embryos and could protect the embryos from apoptosis by inhibiting an apoptotic pathway involving caspases.
authors.affiliation: Department of Obstetrics and Gynecology, Akita University School of Medicine, Akita, 010-8543, Japan. kawamurak@obgyn.med.akita-u.ac.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kawamura
authors.forename: Naoki
authors.initials: N
authors.lastname: Sato
authors.forename: Jun
authors.initials: J
authors.lastname: Fukuda
authors.forename: Hideya
authors.initials: H
authors.lastname: Kodama
authors.forename: Jin
authors.initials: J
authors.lastname: Kumagai
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanikawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001755:Blastocyst / Q000276:immunology / Q000378:metabolism*; D061945:Caspase Inhibitors; D016373:DNA, Antisense; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D051034:Inhibitor of Apoptosis Proteins; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009154:Mutation; D009363:Neoplasm Proteins; D011247:Pregnancy; D012333:RNA, Messenger; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D061945:Caspase Inhibitors; D016373:DNA, Antisense; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000077022:Survivin