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Identification of cytotoxic factors for eggs and development of neutralizing drugs

Research Project

Project/Area Number 26293363
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionNational Center for Child Health and Development

Principal Investigator

MIYADO Kenji  国立研究開発法人国立成育医療研究センター, 細胞医療研究部, 室長 (60324844)

Co-Investigator(Kenkyū-buntansha) 河野 菜摘子  明治大学, 農学部, 講師 (00451691)
Co-Investigator(Renkei-kenkyūsha) INOUE Naokazu (SAITO Hidekazu)  福島県立医科大学, 医学部, 准教授 (90125766)
HAMATANI Toshio  慶應義塾大学, 医学部, 講師 (60265882)
MIYAMOTO YOshitaka  国立成育医療研究センター, 細胞医療研究部, 研究員 (20425705)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2014: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywords卵 / 受精 / 膜融合 / リン脂質 / CD9 / マイクロエクソソーム / エクソソーム / 細胞毒性 / テトラスパニン / ストレス応答 / 再生医学 / 発生 / 細胞 / 脂質 / ストレス / エキソソーム / 顆粒膜細胞 / 老化
Outline of Final Research Achievements

Since CD9 is involved in sperm-egg fusion, this protein may organize membrane architectures. Immunoelectron microscopic analysis revealed that CD9 is incorporated into microexosomes. Since microexosomes have no overt lipid bilayers and seem to be small units, less than 5 nm in diameter, they are structurally different from exosomes. Furthermore, Cd9-deficient eggs could not fuse with sperm, but in the presence of wild-type eggs, 70% of the Cd9-deficient eggs fused with the sperm. Notably, the microexosomes rendered sperm fusion competent with Cd9-deficient eggs, which means that microexosomes, but not the egg microvilli, are essential for sperm-egg fusion. In addition, microexosomes are observed inside the uterus. Taken together, these results indicate that there are two forms of tetraspanin, namely the intercellular transportation-related forms and membrane fusion-related forms.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (32 results)

All 2017 2016 2015 2014

All Journal Article (22 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 22 results,  Open Access: 20 results,  Acknowledgement Compliant: 4 results) Presentation (10 results) (of which Invited: 8 results)

  • [Journal Article] Birth weights and Down syndrome in neonates delivered after frozen-thawed embryo transfer: Six-year study (2007-2012) on the national assisted reproduction registry data in Japan2017

    • Author(s)
      Yamatoya K, Saito K, Saito T, Kang W, Nakamura A, Miyado M, Kawano N, Miyamoto Y, Umezawa A, Miyado K, Saito H
    • Journal Title

      Reproductive Medicine and Biology

      Volume: 16 Issue: 2 Pages: 228-234

    • DOI

      10.1002/rmb2.12033

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exosomes versus microexosomes: Shared components but distinct functions2017

    • Author(s)
      Miyado K, Kang W, Yamatoya K, Hanai M, Nakamura A, Mori T, Miyado M, Kawano N
    • Journal Title

      J Plant Res

      Volume: 130 Issue: 3 Pages: 479-483

    • DOI

      10.1007/s10265-017-0907-7

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Complementary critical functions of Zfy1 and Zfy2 in mouse spermatogenesis and reproductiontran .2017

    • Author(s)
      Nakasuji T, Ogonuki N, Chiba T, Kato T, Shiozawa K, Yamatoya K, Tanaka H, Kondo T, Miyado K, Miyasaka N, Kubota T, Ogura A, Asahara H*.
    • Journal Title

      PLoS Genetics.

      Volume: 13 Issue: 1 Pages: e1006578-e1006578

    • DOI

      10.1371/journal.pgen.1006578

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Expression patterns of Fgf8 and Shh in the developing external genitalia of Suncus murinus2017

    • Author(s)
      Miyado M, Miyado K, Nakamura A, Fukami M, Yamada G, Oda SI
    • Journal Title

      Reproduction

      Volume: 153 Issue: 2 Pages: 187-195

    • DOI

      10.1530/rep-16-0231

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased incidence of post-term delivery and Cesarean section after frozen-thawed embryo transfer during a hormone replacement cycle2016

    • Author(s)
      Saito K, Miyado K, Yamatoya K, Kuwahara A, Inoue E, Miyado M, Fukami M, Ishikawa T, Saito T, Kubota T, Saito H
    • Journal Title

      J Assist Reprod Genet

      Volume: 34 Issue: 4 Pages: 465-470

    • DOI

      10.1007/s10815-017-0869-7

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The p.R92W variant of NR5A1/Nr5a1 induces testicular development of 46,XX gonads in humans, but not in mice: phenotypic comparison of human patients and mutation-induced mice2016

    • Author(s)
      Miyado M, Inui M, Igarashi M, Katoh-Fukui Y, Takasawa K, Hakoda A, Kanno J, Kashimada K, Miyado K, Tamano M, Ogata T, Takada S, Fukami M
    • Journal Title

      Biol Sex Differ

      Volume: 7 Issue: 1 Pages: 56-56

    • DOI

      10.1186/s13293-016-0114-6

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] <b>The role of tetraspanin CD9 in osteoarthritis using three different mouse </b><b>models </b>2016

    • Author(s)
      Sumiyoshi N, Ishitobi H, Miyaki S, Miyado K, Adachi N, Ochi M.
    • Journal Title

      Biomedical Research

      Volume: 37 Issue: 5 Pages: 283-291

    • DOI

      10.2220/biomedres.37.283

    • NAID

      130005432956

    • ISSN
      0388-6107, 1880-313X
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Seminal vesicle proteins SVS3 and SVS4 facilitate SVS2 effect on sperm capacitation2016

    • Author(s)
      Araki N, Yoshida K, Kawano N, Woodin K, Miyado K, Yoshida M
    • Journal Title

      Reproduction

      Volume: 152 Issue: 4 Pages: 313-321

    • DOI

      10.1530/rep-15-0551

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mesenchymal Stem Cell-Derived Exosomes Promote Fracture Healing in a Mouse Model2016

    • Author(s)
      TAISUKE FURUTA, SHIGERU MIYAKI, HIROYUKI ISHITOBI, TOSHIHIKO OGURA, YOSHIO KATO, NAOSUKE KAMEI, KENJI MIYADO, YUKIHITO HIGASHI, MITSUO OCHI
    • Journal Title

      STEM CELLS TRANSLATIONALMEDICINE

      Volume: 5 Issue: 12 Pages: 1620-1630

    • DOI

      10.5966/sctm.2015-0285

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Critical roles of seminal plasma on sperm migration in the female reproductive tract2016

    • Author(s)
      Kang W, Kawano N, Yamatoya K, Yoshida M, Yoshida K, Miyado K
    • Journal Title

      J Reprod Eng

      Volume: 18 Pages: 1-19

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Conditional deletion of CD98hc inhibits osteoclast development.2016

    • Author(s)
      Tsumura H, Ito M, Takami M, Arai M, Li XK, Hamatani T, Igarashi A, Takada S, Miyado K, Umezawa A, Ito Y.
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 5 Pages: 203-210

    • DOI

      10.1016/j.bbrep.2015.11.023

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epididymal C4b-binding protein is processed and degraded during transit through the duct and is not essential for fertility2015

    • Author(s)
      Mayumi I Nonaka, Eva Zsigmond, Akihiko Kudo, Hayato Kawakami, Kaoru Yoshida, Manabu Yoshida, Natsuko Kawano, Kenji Miyado, Masaru Nonaka, Rick A Wetsel
    • Journal Title

      Immunobiology

      Volume: 220(4) Pages: 467-475

    • DOI

      10.1016/j.reth.2015.11.001

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Parturition failure in mice lacking Mamld1.2015

    • Author(s)
      Miyado M, Miyado K, Katsumi M, Saito K, Nakamura A, Shihara D, Ogata T, Fukami M.
    • Journal Title

      Scientific Reports

      Volume: 5 Issue: 1 Pages: 14705-14705

    • DOI

      10.1038/srep14705

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Xenogeneic-free defined conditions for derivation and expansion of human embryonic stem cells with mesenchymal stem cells.2015

    • Author(s)
      Akutsu H, Machida M, Kanzaki S, Sugawara T, Ohkura T, Nakamura N, Yamazaki-Inoue M, Miura T, Vemuri MC, Rao MS, Miyado K, Umezawa A.
    • Journal Title

      Regenerative Therapy

      Volume: 1 Pages: 18-29

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Staphylococcus epidermidis is involved in a mechanism for female reproduction in mice.2015

    • Author(s)
      Ono C, Yoshida M, Kawano N, Miyado K, Umezawa A.
    • Journal Title

      Regenerative Therapy

      Volume: 1 Pages: 11-17

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Phosphorus-insufficient maternal milk is associated with ectopic expression of collagen I and female-specific bony changes in infant mouse cartilages.2015

    • Author(s)
      Nakamura A, Miyado K, Nasu M, Kono T, Umezawa A.
    • Journal Title

      Regenerative Therapy

      Volume: 1 Pages: 5-10

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Seminal Vesicle Secretion 2 Acts as a Protectant of Sperm Sterols and Prevents Ectopic Sperm Capacitation in Mice2014

    • Author(s)
      N Araki, G Trencsenyi, ZT Krasznai, E Nizsaloczki, A Sakamoto, N Kawano, Kenji Miyado, Kaoru Yoshida, Manabu Yoshida
    • Journal Title

      Biology of Reproduction

      Volume: 114 Issue: 1 Pages: 120642-120642

    • DOI

      10.1095/biolreprod.114.120642

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epididymal C4b-binding protein is processed and degraded during transit through the duct and is not essential for fertility2014

    • Author(s)
      MI Nonaka, E Zsigmond, A Kudo, H Kawakami, K Yoshida, N Kawano, K Miyado, M Nonaka, RA Wetsel
    • Journal Title

      Immunobiology

      Volume: 220 Issue: 4 Pages: 467-475

    • DOI

      10.1016/j.imbio.2014.11.001

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mitochondrial Fission Factor Drp1 Maintains Oocyte Quality via Dynamic Rearrangement of Multiple Organelles2014

    • Author(s)
      O Udagawa, T Ishihara, M Maeda, Y Matsunaga, S Tsukamoto, N Kawano, K Miyado, H Shitara, S Yokota, M Nomura, K Mihara, N Mizushima, N Ishihara
    • Journal Title

      Current Biology

      Volume: 24 Issue: 20 Pages: 2451-2458

    • DOI

      10.1016/j.cub.2014.08.060

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mitochondrial dynamics controlled by mitofusins define organelle positioning and movement during mouse oocyte maturation2014

    • Author(s)
      Takuya Wakai, Yuichirou Harada, Kenji Miyado, Tomohiro Kono
    • Journal Title

      Molecular Human Reproduction

      Volume: 20 Issue: 11 Pages: 1090-1100

    • DOI

      10.1093/molehr/gau064

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Absence of CD9 reduces endometrial VEGF secretion and impairs uterine repair after parturition2014

    • Author(s)
      N Kawano, K Miyado, N Yoshii, S Kanai, H Saito, M Miyado, N Inagaki, Y Odawara, T Hamatani, A Umezawa
    • Journal Title

      Scientific reports

      Volume: 4 Issue: 1 Pages: 4701-4701

    • DOI

      10.1038/srep04701

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Derivation of human decidua-like cells from amnion and menstrual blood2014

    • Author(s)
      Sugawara K, Hamatani T, Yamada M, Ogawa S, Kamijo S, Kuji N, Akutsu H, Miyado K, Yoshimura Y, Umezawa A
    • Journal Title

      Sci Rep

      Volume: 4 Issue: 1 Pages: 4599-4599

    • DOI

      10.1038/srep04599

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 卵に対する細胞障害性因子の同定と対処法の開発2016

    • Author(s)
      宮戸健二
    • Organizer
      第34回日本受精着床学会総会・学術講演会
    • Place of Presentation
      軽井沢
    • Year and Date
      2016-09-15
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 精漿タンパク質SVS2欠損マウスから見えて来た、精子を殺すメスの免疫機構2015

    • Author(s)
      河野菜摘子、康宇鎭、吉田薫、吉田学、宮戸健二
    • Organizer
      第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会、ワークショップ:「生殖」から読み解く哺乳類の生命現象(オーガナイザー:深見真紀、宮戸健二)
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] テトラスパニン/エキソソームによる膜融合の制御機構2015

    • Author(s)
      宮戸健二、大和屋健二、河野菜摘子
    • Organizer
      日本動物学会第86回新潟大会
    • Place of Presentation
      朱鷺メッセ:新潟コンベンションセンター
    • Year and Date
      2015-09-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] 哺乳類における配偶子融合の分子機構2015

    • Author(s)
      大和屋健二、宮戸健二、河野菜摘子
    • Organizer
      日本動物学会第86回新潟大会
    • Place of Presentation
      朱鷺メッセ:新潟コンベンション
    • Year and Date
      2015-09-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] 卵由来エキソソームによる配偶子融合の制御機構2015

    • Author(s)
      宮戸健二
    • Organizer
      日本獣医解剖学会シンポジウム
    • Place of Presentation
      北里大学獣医学部
    • Year and Date
      2015-09-07
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Genesis of life: A mechanism of sperm-egg fusion in mammals.2015

    • Author(s)
      Kenji Miyado, Kenji Yamatoya, Natsuko Kawano.
    • Organizer
      日本植物学会第79回大会 シンポジウム: “Fusion” in Fertilization: Interdisciplinary Collaboration among Plant and Animal Scientists
    • Place of Presentation
      朱鷺メッセ:新潟コンベンションセンター
    • Year and Date
      2015-09-06
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 受精における副生殖腺の役割2015

    • Author(s)
      宮戸健二
    • Organizer
      日本生殖医学会学術講演会 シンポジウム3受精に関する最近の話題
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2015-04-27
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] メス生殖器における精子サバイバル術2014

    • Author(s)
      河野菜摘子、荒木直也、吉田薫、吉田学、宮戸健二
    • Organizer
      日本動物学会
    • Place of Presentation
      東北大学川内北キャンパス
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 男と女の生存競争-子宮内での精子の細胞死と防御システム2014

    • Author(s)
      宮戸健二
    • Organizer
      日本アンドロロジー学会
    • Place of Presentation
      軽井沢プリンスホテルウエスト
    • Year and Date
      2014-06-12 – 2014-06-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 河野菜摘子、宮戸健二、吉田薫、吉田学2014

    • Author(s)
      新たに見つかった子宮内での精子保護機構
    • Organizer
      日本アンドロロジー学会
    • Place of Presentation
      軽井沢プリンスホテルウエスト
    • Year and Date
      2014-06-12 – 2014-06-13
    • Related Report
      2014 Annual Research Report
    • Invited

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Published: 2014-04-04   Modified: 2018-03-22  

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