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Genes expressed specifically in oocytes may have an important role in the quality (developmental competence) of oocytes

Research Project

Project/Area Number 19591911
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKeio University

Principal Investigator

HAMATANI Toshio  Keio University, 医学部, 講師 (60265882)

Co-Investigator(Kenkyū-buntansha) YOSHIMURA Yasunori  慶應義塾大学, 医学部, 教授 (10129736)
AKUTSU Hidenori  国立成育医療センター研究所, 生殖医療研究部, 室長 (50347225)
YAMADA Mitsutoshi  国立成育医療センター研究所, 生殖医療研究部, 研究員 (40383864)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords生殖医学 / 卵 / 胚性幹細胞 / 着床前期胚 / 遺伝子発現プロファイリング / RNAi / トランスジェニック・マウス
Research Abstract

To elucidate molecular mechanisms underlying oogenesis and oocyte quality, we first employed in silico analysis of global gene expression profiling data and an EST frequency database, and selected genes that are specifically expressed in oocytes and preimplantation embryos. We further studied the differences of gene expression profiles (1) between oocytes from aged mice and those from young mice, and (2) between post-ovulatory aged oocytes and fresh oocytes to extract genes that are important for oocyte quality. Finally, we focused on two oocyte-specific gene families (Nlrp [NACHT, leucine-rich repeat and PYD containing] genes and KRAB [Kruppel-associated box] zinc finger genes).
As results of quantitative RT-PCR and in situ hybridization assays, we confirmed oocyte-specific expression of the Nlrp and the KRAB genes at the follicle stages later than the primary-follicle stage. To analyze gene function of the Nlrp genes, we used the RNA interference approach : injection with siRNAs into … More mouse fertilized eggs. The knockdown of a Nlrp gene lead to cleavage arrest during preimplantation development. On the other hand, we are now in the process of generating knockout mice for an oocyte-specific KRAB zinc finger gene.
In addition, we study a preimplantation-stage-specific gene Hmgpi which is a putative chromosomal protein with two high-mobility-group boxes. Hmgpi is zygotically transcribed during zygotic genome activation, but not transcribed after implantation. The Hmgpi-encoded protein (HMGPI), first detected at the 4-cell stage, remains highly expressed in pre-implantation embryos. Interestingly, HMGPI is expressed in both the inner cell mass (ICM) and the trophectoderm, and translocated from cytoplasm to nuclei at the blastocyst stage, indicating differential spatial requirements before and after the blastocyst stage. siRNA (siHmgpi)-induced reduction of Hmgpi transcript levels caused developmental loss of preimplantation embryos and implantation failures. Furthermore, reduction of Hmgpi prevented blastocyst outgrowth leading to generation of embryonic stem cells. The siHmgpi-injected embryos also lost ICM and trophectoderm integrity, demarcated by reduced expressions of Oct4, Nanog and Cdx2. The findings implicated an important role for Hmgpi at the earliest stages of mammalian embryonic development. Less

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (32 results)

All 2010 2009 2008 2007

All Journal Article (16 results) (of which Peer Reviewed: 13 results) Presentation (14 results) Book (2 results)

  • [Journal Article] A Acute stress may induce ovulation in women2010

    • Author(s)
      Tarin JJ, Hamatani T, Cano
    • Journal Title

      Reprod Biol Endocrinol (in press)

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chip to analyze cell identity in Reproductive and Regenerative Medicine2010

    • Author(s)
      Toyoda M, Hamatani T, Matsumoto K, Saito H, Umezawa A
    • Journal Title

      Current Medicinal Chemistry (in press)

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of a novel preimplantation-specific gene encoding the high mobility group box protein Hmgpi in early embryonic development2010

    • Author(s)
      Yamada M, Hamatani T, Akutsu H, Chikazawa N, Kuji N, Yoshimura Y, Umezawa A
    • Journal Title

      Human Molecular Genetics 19(3)

      Pages: 480-493

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of a novel preimplantation-specific gene encoding the high mobility group box protein Hmgpi in early embryonic development2010

    • Author(s)
      Yamada M, Hamatani T, Akutsu H, Chikazawa N, Kuji N, Yoshimura Y, Umezawa A.
    • Journal Title

      Human Molecular Genetics 19(3)

      Pages: 480-493

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article]2009

    • Author(s)
      浜谷敏生, 山田満稔, 吉村泰典
    • Journal Title

      よくわかる病態生理(監修:松尾理)第12巻婦人科疾患【構造と機能】女性生殖器の発育過程, 性周期発現と排卵の機序(編集:久保田俊郎)(日本医事新報社, 東京)

    • Related Report
      2009 Annual Research Report
  • [Journal Article] What can you 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 M, Umezawa A, Kuji N, Yoshimura Y
    • Journal Title

      Reproduction 135(5)

      Pages: 581-592

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Buoyant density and sedimentation dynamics of HIV-1 in two density-gradient media for semen processing2008

    • Author(s)
      Kuji N, Yoshii T, Hamatani T, Hanabusa H, Yoshimura Y, Kato S
    • Journal Title

      Fertlity and Sterility 90(5)

      Pages: 1983-1987

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] 遺伝子発現プロファイリングによる卵の加齢機構の探索2008

    • Author(s)
      浜谷敏生
    • Journal Title

      日本産科婦人科学会雑誌(Acta Obst Gynaec JPN) 60(10)

      Pages: 1798-1812

    • NAID

      110006951085

    • Related Report
      2009 Final Research Report
  • [Journal Article] What can you 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 M, Umezawa A, Kuji N, Yoshimura Y.
    • Journal Title

      Reproduotion 135(5)

      Pages: 581-592

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Buoyant density and sedimentation dynamics of HIV-1 in two density-gradient media for semen processing.2008

    • Author(s)
      Kuji N, Yoshii T, Hamatani T, Hanabusa H, Yoshimura Y, Kato S.
    • Journal Title

      Fertlity and Sterility 90(5)

      Pages: 1983-1987

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 遺伝子発現プロフアイリングによる卵の加齢機構の探索2008

    • Author(s)
      浜谷敏生
    • Journal Title

      日本産科婦人科学会雑誌Acta Obst Gynaec JPN 60(10)

      Pages: 1798-1812

    • Related Report
      2008 Annual Research Report
  • [Journal Article] What can you learn from gene expression profiling of mouse oocytes2008

    • Author(s)
      Hamatani T, Yamada M, Akutsu H, Kuji N, Mochimaru Y, Takano M, Toyoda M, Miyado M, Umezawa A, Kuji N, Yoshimura Y.
    • Journal Title

      Reproduction 135(5)

      Pages: 581-592

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Elimination of HIV-1 from semen and application of the processed semen to assisted reproductive technologiy2007

    • Author(s)
      Kuji N, Mizusawa Y, Naganishi M, Hamatani T, Iwata S, Yoshimura Y
    • Journal Title

      Reproductive Medicine and Biology 6(3)

      Pages: 151-156

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Zscan4: a novel gene expressed exclusively in late 2-cell embryos and embryonic stem cells2007

    • Author(s)
      Falco G, Lee SL, Stanghellini I, Bassey UC, Hamatani T, Ko MSH
    • Journal Title

      Developmental Biology 307(2)

      Pages: 539-550

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Elimination of HIV-1 from semen and application of the processed semen to assisted reproductive technologiy2007

    • Author(s)
      Kuji N, Mizusawa Y, Naganishi M, Hamatani T, Iwata S, Yoshimura Y.
    • Journal Title

      Reproductive Medicine and Biology 6(3)

      Pages: 151-156

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Zscan4:a novel gene expressed exclusively in late 2-cell embryos and embryonic stem cells2007

    • Author(s)
      Falco G, Lee SL, Stanghellini I, Bassey UC, Hamatani T, Ko MSH.
    • Journal Title

      Developmental Biology 307(2)

      Pages: 539-550

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] 着床前期特異的新規遺伝子Hmgpによる着床周辺期発生の制御機構2009

    • Author(s)
      山田満稔, 浜谷敏生, 阿久津英憲, 持丸佳之, 高野光子, 浅田弘法, 久慈直昭, 吉村泰典
    • Organizer
      第54回日本生殖医学会・学術講演会
    • Place of Presentation
      金沢
    • Year and Date
      2009-11-23
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] 単一卵子のDNAマイクロアレイによる遺伝子発現解析とその応用2009

    • Author(s)
      持丸佳之, 久慈直昭, 山田満稔, 高野光子, 浜谷敏生, 阿久津英憲, 浅田弘法, 末岡浩, 青木大輔, 吉村泰典
    • Organizer
      第27回日本受精着床学会
    • Place of Presentation
      京都
    • Year and Date
      2009-08-06
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] 着床前期胚に特異的に発現する新規遺伝子Hmgpの発現および機能解析2009

    • Author(s)
      山田満稔, 浜谷敏生, 阿久津英憲, 持丸佳之, 高野光子, 浅田弘法, 久慈直昭, 青木大輔, 梅澤明弘, 吉村泰典
    • Organizer
      第50回日本哺乳動物卵子学会
    • Place of Presentation
      東京
    • Year and Date
      2009-05-08
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] 交流磁場発生装置を用いたブタ卵巣の超低温保存2009

    • Author(s)
      持丸佳之, 久慈直昭, 高野光子, 浜谷敏生, 浅田弘法, 青木大輔, 吉村泰典
    • Organizer
      第61回日本産科婦人科学会総会・学術講演会
    • Place of Presentation
      京都
    • Year and Date
      2009-04-04
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] マウス卵特異的新規Krab-zinc finger遺伝子の発現解析2008

    • Author(s)
      山田満稔, 浜谷敏生, 阿久津英憲, 持丸佳之, 高野光子, 浅田弘法, 久慈直昭, 吉村泰典
    • Organizer
      第53回日本生殖医学会学術講演会
    • Place of Presentation
      神戸
    • Year and Date
      2008-10-24
    • Related Report
      2009 Final Research Report 2008 Annual Research Report
  • [Presentation] 生殖医学のトピックス:遺伝子発現プロファイリングによる卵の正常性の検討2008

    • Author(s)
      浜谷敏生
    • Organizer
      第26回日本ヒト細胞学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2008-08-30
    • Related Report
      2009 Final Research Report
  • [Presentation] シンポジウム : 生殖医学のトピックス : 遺伝子発現プロフアイリングによる卵の正常性の検討2008

    • Author(s)
      浜谷敏生
    • Organizer
      第26回日本ヒト細胞学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2008-08-30
    • Related Report
      2008 Annual Research Report
  • [Presentation] 卵の発育・成熟・老化機構の解明と臨床応用:遺伝子発現プロファイリングによる卵の加齢機構の探索2008

    • Author(s)
      浜谷敏生
    • Organizer
      第60回日本産科婦人科学会総会・学術講演会
    • Place of Presentation
      横浜
    • Year and Date
      2008-04-15
    • Related Report
      2009 Final Research Report
  • [Presentation] シンポジウム : 卵の発育・成熟・老化機構の解明と臨床応用遺伝子発現プロフアイリングによる卵の加齢機構の探索2008

    • Author(s)
      浜谷敏生
    • Organizer
      第60回日本産科婦人科学会総会・学術講演会
    • Place of Presentation
      横浜
    • Year and Date
      2008-04-15
    • Related Report
      2008 Annual Research Report
  • [Presentation] マウス卵特異的新規Homeobox遺伝子の発現解析2007

    • Author(s)
      山田満稔, 浜谷敏生, 阿久津英憲, 浅田弘法, 久慈直昭, 吉村泰典
    • Organizer
      第52回日本生殖医学会総会・学術講演会
    • Place of Presentation
      秋田
    • Year and Date
      2007-10-25
    • Related Report
      2009 Final Research Report 2007 Annual Research Report
  • [Presentation] Identification of a novel gene encoding a b-box zinc finger protein with its specific expression and essential role during preimplantation development2007

    • Author(s)
      Yamada M, Hamatani T, Akutsu H, Kuji N, Umezawa A, Yoshimura Y
    • Organizer
      The 63th Annual Meeting of the American Society for Reproductive Medicine
    • Place of Presentation
      Washington DC
    • Year and Date
      2007-10-16
    • Related Report
      2009 Final Research Report
  • [Presentation] Identification of a novel gene encoding a b-box zinc finger protein with its specific expression and essential role during Preimplantation development2007

    • Author(s)
      Yamada M, Hamatani T, Akutsu H, Kuji N, Umezawa A, Yoshimura Y
    • Organizer
      The 63th Annual Meeting of the American Society for Reproductive Medicine
    • Place of Presentation
      Washington DC
    • Year and Date
      2007-10-16
    • Related Report
      2007 Annual Research Report
  • [Presentation] マウス新規ホメオボックス遺伝子の卵細胞・着床前期胚における発現特異性2007

    • Author(s)
      山田満稔, 浜谷敏生, 阿久津英憲, 水澤友利, 庄司真弓, 羽田智則, 浅田弘法, 久慈直昭, 青木大輔, 吉村泰典
    • Organizer
      第59階日本産科婦人科学会学術講演会
    • Place of Presentation
      京都
    • Year and Date
      2007-04-16
    • Related Report
      2009 Final Research Report
  • [Presentation] マウス新規ホメオボックス遺伝子の卵細胞・着床前期胚における発現特異性2007

    • Author(s)
      山田 満稔、浜谷 敏生、阿久津 英憲、水澤 友利、庄司 真弓、羽田 智則、浅田 弘法、久慈 直昭、青木 大輔、吉村 泰典
    • Organizer
      弟59階日本産科婦人科学会学術講演会
    • Place of Presentation
      京都
    • Year and Date
      2007-04-16
    • Related Report
      2007 Annual Research Report
  • [Book] よくわかる病態生理(監修:松尾理)第12巻婦人科疾患(編集:久保田俊郎)【構造と機能】女性生殖器の発育過程.性周期発現と排卵の機序2009

    • Author(s)
      浜谷敏生,山田満稔,吉村泰典
    • Publisher
      日本医事新報社
    • Related Report
      2009 Final Research Report
  • [Book] よくわかる病態生理(監修 : 松尾理)第12巻婦人科疾患(編集 : 久保田俊郎)【構造と機能】女性生殖器の発育過程. 性周期発現と排卵の機序.2009

    • Author(s)
      浜谷敏生, 山田満稔, 吉村泰典.
    • Publisher
      日本医事新報社
    • Related Report
      2008 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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