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466 results on '"TANAKA, TOSHINOBU"'

5. Regulation of preimplantation embryo development by brain-derived neurotrophic factor

Author

Kawamura, Kazuhiro, Kawamura, Nanami, Fukuda, Jun, Kumagai, Jin, Hsueh, Aaron J.W., and Tanaka, Toshinobu

Subjects
Embryo, Growth factors, Biological sciences
Abstract

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2007.08.026 Byline: Kazuhiro Kawamura (a)(c), Nanami Kawamura (a)(b), Jun Fukuda (a), Jin Kumagai (a), Aaron J.W. Hsueh (c), Toshinobu Tanaka (a) Keywords: Apoptosis; BDNF; Blastocyst; ERK; NT-4/5; PI3K; TrkB Abstract: Hormonal factors secreted by embryos and reproductive tracts are important for successful development of preimplantation embryos. We found expression of brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5) transcripts at its highest levels in the blastocyst stages. The transcripts for their receptor, TrkB, were detectable throughout the early embryonic stages with an increase after the early blastocyst stage. Both BDNF and TrkB are expressed in trophectoderm cells, whereas ligand-binding studies indicated specific binding of BDNF to trophectoderm cells. Furthermore, BDNF and NT-4/5 were produced in pregnant oviducts and uteri. Treatment with BDNF promoted the development of two-cell-stage embryos into blastocysts showing increased proliferation and decreased apoptosis. The effects of BDNF were blocked by the TrkB ectodomain or a Trk receptor inhibitor, K252a. Studies using specific inhibitors demonstrated the roles of the PI3K, but not the ERK, pathway in mediating BDNF actions. Under high-density embryo cultures, treatment with the TrkB ectodomain or K252a alone also inhibited embryonic development and survival, suggesting potential autocrine actions of BDNF produced by the embryo. In vivo experiments further demonstrated that K252a treatment suppressed early embryo development by inhibiting blastocyst cell numbers, and increasing blastocyst apoptosis. Our findings suggested that BDNF signaling plays important paracrine roles during blastocyst development by promoting the development of preimplantation embryos. Author Affiliation: (a) Department of Obstetrics and Gynecology, Akita University School of Medicine, Akita, 010-8543, Japan (b) Department of Dermatology and Plastic Surgery, Akita University School of Medicine, Akita, 010-8543, Japan (c) Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305-5317, USA Article History: Received 15 June 2007; Revised 17 July 2007; Accepted 9 August 2007

Published
2007

7. Survivin acts as an antiapoptotic factor during the development of mouse preimplantation embryos

Author

Kawamura, Kazuhiro, Sato, Naoki, Fukuda, Jun, Kodama, Hideya, Kumagai, Jin, Tanikawa, Hideo, Shimizu, Yasushi, and Tanaka, Toshinobu

Subjects
Apoptosis -- Research, Biological sciences
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. Keywords: Apoptosis; Caspase; Development; Preimplantation embryo; Survivin

Published
2003

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