Functional analysis of fusogenic factors related to infertility and its clinical application

2010 Fiscal Year Final Research Report

• Project/Area Number: 19390431
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: National Research Institute for Child Health and Development
• Principal Investigator: MIYADO Kenji National Research Institute for Child Health and Development, 生殖・細胞医療研究部, 室長 (60324844)
• Co-Investigator(Kenkyū-buntansha): AKUTSU Hidenori 独立行政法人国立成育医療研究センター, 生殖・細胞医療研究部, 室長 (50347225)
• Project Period (FY): 2007 – 2010
• Keywords: 生殖医学

Research Abstract

Membrane fusion is an essential step in the encounter of two nuclei from sperm and egg in fertilization. Here, we showed that sperm-egg fusion is mediated by vesicles containing CD9 that are released from the egg and interact with sperm.

Research Products

• [Journal Article] Lipid rafts enriched in monosialylGb5Cer carrying the stage-specific embryonic antigen-4 epitope are involved in development of mouse preimplantation embryos at cleavage stage. (2011)
  • Author(s): Sato B, Katagiri YU, Miyado K, Okino N, Ito M, Akutsu H, Okita H, Umezawa A, Fujimoto J, Toshimori K, Kiyokawa N.
  • Journal Title: BMC Dev Biol. Pages: 11-22
  • Peer Reviewed
• [Journal Article] Role of CD9 and CD9-containing exosomes in sperm-egg membrane fusion. (2010)
  • Author(s): Kawano N., Yoshida K., Harada Y., Onami N., Takezawa Y., Miyado K.
  • Journal Title: J Mamm Ova Res. 27(4) Pages: 191-197
• [Journal Article] Age-associated changes in the subcellular localization of phosphorylated p38 MAPK in human granulosa cells. (2010)
  • Author(s): Ito M, Miyado K, Nakagawa K, Muraki M, Imai M, Yamakawa N, Qin J, Hosoi Y, Saito H, Takahashi Y.
  • Journal Title: Mol Hum Reprod. 16(12) Pages: 928-37
  • Peer Reviewed
• [Journal Article] Mice lacking two sperm serine proteases, ACR and PRSS21, are subfertile, but the Mutant Sperm are infertile in vitro. (2010)
  • Author(s): Kawano N., Kang W., Yamashita M., Koga Y., Yamazaki T., Hata T., Miyado K., Baba T.
  • Journal Title: Biol Reprod. 83(3) Pages: 359-69
  • Peer Reviewed
• [Journal Article] Xenografted human amniotic membrane-derived mesenchymal stem cells were immunologically tolerated and transdifferentiated into cardiomyocytes. (2010)
  • Author(s): Tsuji H, Miyoshi S, Ikegami Y, Hida N, Asada H, Togashi I, Suzuki J, Satake M, Nakamizo H, Tanaka M, Mori T, Segawa K, Nishiyama N, Inoue J, Makino H, Miyado K, Ogawa S, Yoshimura Y, Umezawa A.
  • Journal Title: Circulation Res 106(10) Pages: 1613-23
  • Peer Reviewed
• [Journal Article] Tetraspanin family protein CD9 in the mouse sperm : unique localization, appearance, behavior and fate during fertilization. (2010)
  • Author(s): Ito C, Yamatoya K, Yoshida K, Maekawa M, Miyado K, Toshimori K.
  • Journal Title: Cell Tissue Res. 340(3) Pages: 583-94
  • Peer Reviewed
• [Journal Article] Serum-independent cardiomyogenic transdifferentiation in human endometrium-derived mesenchymal cells. (2010)
  • Author(s): Ikegami Y, Miyoshi S, Nishiyama N, Hida N, Okamoto K, Miyado K, Segawa K, Ogawa S, Umezawa A.
  • Journal Title: Artif Organs 34(4) Pages: 280-8
  • Peer Reviewed
• [Journal Article] Maintenance of pluripotency and self-renewal ability of mouse embryonic stem cells in the absence of tetraspanin CD9. (2009)
  • Author(s): Akutsu H, Miura T, Machida M, Birumachi JI, Hamada A, Yamada M, Sullivan S, Miyado K, Umezawa A.
  • Journal Title: Differentiation 78(2-3) Pages: 137-42
  • Peer Reviewed
• [Journal Article] Equatorin : Identification and Characterization of the Epitope of the MN9 Antibody in the Mouse. (2009)
  • Author(s): Yamatoya K, Yoshida K, Ito C, Maekawa M, Yanagida M, Takamori K, Ogawa H, Araki Y, Miyado K, Toyama Y, Toshimori K.
  • Journal Title: Biol Reprod 81(5) Pages: 889-97
  • Peer Reviewed
• [Journal Article] Shortening of human cell life span by induction of p16ink4a through the platelet-derived growth factor receptor beta. (2009)
  • Author(s): Takahashi H, Toyoda M, Birumachi J, Horie A, Uyama T, Miyado K, Matsumoto K, Saito H, Umezawa A.
  • Journal Title: J Cell Physiol 221(2) Pages: 335-42
  • Peer Reviewed
• [Journal Article] The fusing ability of sperm is bestowed by CD9-containing vesicles released from eggs in mice. (2008)
  • Author(s): Miyado K, Yoshida K, Yamagata K, Sakakibara K, Okabe M, Wang X, Miyamoto K, Akutsu H, Kondo T, Takahashi Y, Ban T, Ito C, Toshimori K, Nakamura A, Ito M, Miyado M, Mekada E, Umezawa A.
  • Journal Title: Proc Natl Acad Sci USA(Miyado K is a corresponding author; Faculty of 1000 Biology推薦論文) 105(35) Pages: 12921-6
  • Peer Reviewed
• [Journal Article] Double deficiency of tetraspanins CD9 and CD81 alters cell motility and protease production of macrophages and causes chronic obstructive pulmonary disease-like phenotype in mice. (2008)
  • Author(s): Takeda Y, He P, Tachibana I, Zhou B, Miyado K, Kaneko H, Suzuki M, Minami S, Iwasaki T, Goya S, Kijima T, Kumagai T, Yoshida M, Osaki T, Komori T, Mekada E, Kawase I.
  • Journal Title: J Biol Chem 283(38) Pages: 26089-97
  • Peer Reviewed
• [Journal Article] Functional significance of stage-specific embryonic antigens in the development of preimplantation embryos. (2008)
  • Author(s): Katagiri Y, Sato B, Miyado K, Akutsu H, Okita H, Umezawa A, Fujimoto J, Kiyokawa N.
  • Journal Title: Trends in Glycoscience and Glycotechnology 20(113) Pages: 131-39
  • Peer Reviewed
• [Journal Article] Novel cardiac precursor-like cells from human menstrual blood-derived mesenchymal cells. (2008)
  • Author(s): Hida N, Nishiyama N, Miyoshi S, Kira S, Segawa K, Uyama T, Mori T, Miyado K, Ikegami Y, Cui C, Kiyono T, Kyo S, Shimizu T, Okano T, Sakamoto M, Ogawa S, Umezawa A.
  • Journal Title: Stem Cells 26(7) Pages: 1695-704
  • Peer Reviewed
• [Journal Article] What can we learn from gene expression profiling of mouse oocytes? (2008)
  • Author(s): Hamatani T, Yamada M, Akutsu H, Kuji N, Mochimaru Y, Takano M, Toyoda M, Miyado K, Umezawa A, Yoshimura Y.
  • Journal Title: Reproduction 135(5) Pages: 581-92
  • Peer Reviewed
• [Journal Article] Possible involvement of CD81 in acrosome reaction of sperm in mice. (2008)
  • Author(s): Tanigawa M, Miyamoto K, Kobayashi S, Sato M, Akutsu H, Okabe M, Mekada E, Umezawa A, Miyado K.
  • Journal Title: Mol Reprod Dev(Miyado K is a corresponding author) 75(1) Pages: 150-5
  • Peer Reviewed
• [Journal Article] Glutathione S-transferase theta 1 expressed in granulosa cells as a biomarker for oocyte quality in age-related infertility. (2008)
  • Author(s): Ito M, Muraki M, Takahashi Y, Imai M, Tsukui T, Yamakawa N, Nakagawa K, Ohgi S, Horikawa T, Iwasaki W, Iida A, Nishi Y, Yanase T, Nawata H, Miyado K, Kono T, Hosoi Y, Saito H.
  • Journal Title: Fertil Steril 90(4) Pages: 1026-35
  • Peer Reviewed
• [Journal Article] Preferential localization of SSEA-4 in interfaces between blastomeres of mouse preimplantaion embryos. (2007)
  • Author(s): Sato B, Katagiri YU, Miyado K, Akutsu H, Miyagawa Y, Horiuchi Y, Nakajima H, Okita H, Umezawa A, Hata J, Fujimoto J, Toshimori K, Kiyokawa N.
  • Journal Title: Biochem Biophys Res Commun 364(4) Pages: 838-43
  • Peer Reviewed
• [Journal Article] Sonic hedgehog expression during early tooth development in Suncus murinus. (2007)
  • Author(s): Miyado M, Ogi H, Yamada G, Kitoh J, Jogahara T, Oda S, Sato I, Miyado K, Sunohara M.
  • Journal Title: Biochem Biophys Res Commun 363(2) Pages: 269-75
  • Peer Reviewed
• [Journal Article] 'Working' cardiomyocytes exhibiting plateau action potentials from human placenta-derived extraembryonic mesodermal cells. (2007)
  • Author(s): Okamoto K, Miyoshi S, Toyoda M, Hida N, Ikegami Y, Makino H, Nishiyama N, Tsuji H, Cui CH, Segawa K, Uyama T, Kami D, Miyado K, Asada H, Matsumoto K, Saito H, Yoshimura Y, Ogawa S, Aeba R, Yozu R, Umezawa A.
  • Journal Title: Exp Cell Res 313(12) Pages: 2550-62
  • Peer Reviewed
• [Journal Article] The significant cardiomyogenic potential of human umbilical cord blood-derived mesenchymal stem cells in vitro. (2007)
  • Author(s): Nishiyama N, Miyoshi S, Hida N, Uyama T, Okamoto K, Ikegami Y, Miyado K, Segawa K, Terai M, Sakamoto M, Ogawa S, Umezawa A.
  • Journal Title: Stem Cells 25(8) Pages: 2017-24
  • Peer Reviewed
• [Journal Article] Menstrual blood-derived cells confer human dystrophin expression in the murine model of Duchenne muscular dystrophy via cell fusion and myogenic transdifferentiation. (2007)
  • Author(s): Cui CH, Uyama T, Miyado K, Terai M, Kyo S, Kiyono T, Umezawa A.
  • Journal Title: Mol Biol Cell 18(5) Pages: 1586-94
  • Peer Reviewed
• [Journal Article] Hyaline cartilage formation and enchondral ossification modeled with KUM5 and OP9 chondroblasts. (2007)
  • Author(s): Sugiki T, Uyama T, Toyoda M, Morioka H, Kume S, Miyado K, Matsumoto K, Saito H, Tsumaki N, Takahashi Y, Toyama Y, Umezawa A.
  • Journal Title: J Cell Biochem 100(5) Pages: 1240-54
  • Peer Reviewed
• [Journal Article] Lipid Rafts : Keys to SpermMaturation, Fertilization, and Early Embryogenesis.
  • Author(s): Kawano N, Yoshida K, Miyado K, Yoshida M.
  • Journal Title: Journal of Lipids in press
  • Peer Reviewed
• [Presentation] Arrest of spermatogenesis at round spermatids in PLCZ1-deficient mice. (2010)
  • Author(s): Ito M, Nagaoka K, Kuroda K, Kawano N, Yoshida K, Harada, Y, Shikano T, Miyado M, Oda S, Toshimori K, Mizukami Y, Murata T, Umezawa A, Miyazaki S, Miyado K.
  • Organizer: Symposium : Sperm formation and differentiation, 11th International Symposium on Spermatology
  • Year and Date: 20100624-20100629
• [Presentation] The essential role of seminal vesicle secretions on the sperm fertility in the female reproductive tract. (2010)
  • Author(s): Kawano N, Araki N, Yoshida K, Yoshida M, Miyado K.
  • Organizer: 11th International Symposium on Spermatology
  • Year and Date: 20100624-20100629
• [Presentation] Signal transduction and function of sperm citrate synthase as a sperm factor in vertebrate fertilization. (2010)
  • Author(s): Harada Y, Iwao Y, Miyado K.
  • Organizer: 11th International Symposium on Spermatology
  • Year and Date: 20100624-20100629
• [Presentation] Ablation of beta-catenin suppresses membrane localization of E-cadherin and reduces the ability of membrane adhesion with sperm in moue eggs. (2010)
  • Author(s): Takezawa Y, Nakamura A, Sakakibara K, Kawano N, Harada Y, Yoshida K, Umezawa A, Miyado K.
  • Organizer: 11th International Symposium on Spermatology
  • Year and Date: 20100624-20100629
• [Presentation] 哺乳動物における配偶子融合の分子認証機構.シンポジウム「植物から学ぶ受精機構:動植物共通のアロ認証機構を考える (2010)
  • Author(s): 宮戸健二
  • Organizer: 第81回日本動物学会大会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-24
• [Presentation] 受精の膜融合における卵側因子CD9とエキソソームの役割 (2009)
  • Author(s): 宮戸健二
  • Organizer: ワークショップ「動植物におけるアロ認証機構」第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 20091209-20091212
• [Presentation] 受精の膜融合におけるCD9のユニークで不可欠な挙動 (2009)
  • Author(s): 河野菜摘子、宮戸健二
  • Organizer: ワークショップ「テトラスパニン研究の新展開」第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 20091209-20091212
• [Presentation] 受精の膜融合における卵側因子CD9とエキソソームの役割 (2009)
  • Author(s): 宮戸健二
  • Organizer: シンポジウム「動植物におけるアロ認証機構」第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 20091021-20091024
• [Presentation] 膜融合を制御するテトラスパニンの役割:受精からのアプローチ (2009)
  • Author(s): 河野菜摘子、宮戸健二
  • Organizer: シンポジウム「テトラスパニンの生化学」第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 20091021-20091024
• [Presentation] CD9 action in the egg and on the sperm of mice. (2009)
  • Author(s): 宮戸健二
  • Organizer: Cell-Cell Fusion Gordon Research Conference
  • Place of Presentation: New London
  • Year and Date: 2009-07-19
• [Book] VI-12歯胚形成過程におけるsShh遺伝子の発現 (2011)
  • Author(s): 宮戸真美、尾木秀直、城ヶ原貴通、織田銑一、宮戸健二
  • Publisher: 「スンクスの生物学」学会出版センター
• [Book] VI-13スンクス雄の外生殖器 (2011)
  • Author(s): 宮戸真美、尾木秀直、織田銑一、宮戸健二
  • Publisher: 「スンクスの生物学」学会出版センター
• [Book] Role of CD9 in sperm-egg fusion and its general role in fusion phenomena, Cell Fusions : Regulation and Control. Larsson, Lars-Inge (ed). (2010)
  • Author(s): Kawano N., Harada Y., Yoshida K., Miyado M., Miyado K.
  • Total Pages: 171-184
  • Publisher: Springer
• [Book] 目で見る生殖に関連したモデル動物-受精障害モデル動物-Hormone Frontier in Gynecology 16 (2009)
  • Author(s): 宮戸健二
  • Total Pages: 2-5
• [Book] 顕微鏡活用なるほどQ&A (2008)
  • Author(s): 岡部勝、宮戸健二編
  • Publisher: 羊土社
• [Book] 生殖における酸化ストレスの生理的役割と不妊症疾患(実験医学26) (2008)
  • Author(s): 高橋祐司、宮戸健二、齋藤英和
  • Total Pages: 586-590
• [Book] 受精卵が作られるしくみ:精子と卵の融合機構の解明(研究報告集23) (2007)
  • Author(s): 宮戸健二
  • Total Pages: 144-156
  • Publisher: 財団法人 三共生命科学研究振興財団
• [Remarks] ホームページ等
  • URL: http://www.ncchd.go.jp/research.php
• [Patent(Industrial Property Rights)] 細胞の造腫瘍性試験方法及び腫瘍マーカー (2010)
  • Inventor(s): 宮戸健二、梅澤明弘
  • Industrial Property Rights Holder: ヒューマンサイエンス財団
  • Industrial Property Number: 特願2010-215828
  • Filing Date: 2010-09-27
• [Patent(Industrial Property Rights)] 哺乳動物卵内への細胞外物質の導入促進剤及び導入方法 (2010)
  • Inventor(s): 阿久津英憲、宮戸真美、宮戸健二
  • Industrial Property Rights Holder: Japan Science and Technology Agency
  • Industrial Property Number: 特許第4448172号
  • Acquisition Date: 2010-01-29
• [Patent(Industrial Property Rights)] Promoter for introducing extracellular substance into mammalian ovum and introduction method (2010)
  • Inventor(s): 阿久津英憲, 宮戸真美, 宮戸健二
  • Industrial Property Rights Holder: Japan Science and Technology Agency
  • Industrial Property Number: 2006242041
  • Acquisition Date: 2010-11-11