The study for development of novel mammalian oocyte culture system generated from microarray data base of ovulating process

• Project/Area Number: 18688016
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Applied animal science
• Research Institution: Hiroshima University
• Principal Investigator: SHIMADA Masayuki Hiroshima University, 大学院・生物圏科学研究科, 准教授 (20314742)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥29,770,000 (Direct Cost: ¥22,900,000、Indirect Cost: ¥6,870,000); Fiscal Year 2008: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000); Fiscal Year 2007: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000); Fiscal Year 2006: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
• Keywords: 卵子 / 排卵 / 受精 / 体外成熟培養 / マイクロアレイ / 遺伝子発現 / 内分泌 / 卵丘細胞 / 成長因子 / 遺伝子改変マウス / サイトカイン / 自然免疫 / 精子 / エキソサイトーシス / プロテアーゼ / siRNA / プロジェステロン / プロスタグランジン

Research Abstract

本研究は,マウス排卵過程における卵胞内の遺伝子発現を経時的にかつ網羅的に解析し,成長因子,サイトカイン類が発現していること,それらが分泌し作用する仕組みを明らかとした.この成果を元に,哺乳動物において自然免疫系が受精を制御していることを初めて解明し,その機能の不全が体外受精における受精率の低下を引き起こすことを示した.さらには,それぞれの生理活性因子の添加時期を最適化した新規体外成熟培養法を考案した.

Research Products

• [Journal Article] ERK1/2 in ovarian granulosa cells are critical for female fertility (2009)
  • Author(s): Fan HY, Liu Z, Shimada M, Sterneck E, Johnson PF, Hedrick SM, Richards JS
  • Journal Title: Science 324 Pages: 938-941
  • Peer Reviewed
• [Journal Article] IL6: an autocrine regulator of the mouse cumulus cell-oocyte complex expansion process (2009)
  • Author(s): Liu Z, de Matos DG, Fan HY, Shimada M, Palmer S, Richards JS
  • Journal Title: Endocrinology doi:10.1210/en Pages: 2008-1532
  • Peer Reviewed
• [Journal Article] ERK1/2 in ovarian granulosa cells are critical for female fertility (2009)
  • Author(s): H. Fan
  • Journal Title: Science (In press)
  • Peer Reviewed
• [Journal Article] Sequential exposure of porcine cumulus cells to FSH and/or LH is critical for appropriate expression of steroidogenic and ovulation related genes that impact oocyte maturation in vivo and in vitro (2008)
  • Author(s): Kawashima I, Okazaki T, Noma N, Nishibori M, Yamashita Y, Shimada M
  • Journal Title: Reproduction vol. 136 (1) Pages: 9-21
  • Peer Reviewed
• [Journal Article] Somatic Expression of K-rasG12D in mouse ovary causes defects of follicle development and ovulation (2008)
  • Author(s): Fan HY, Shimada M, Liu Z, Cahill N, Noma N, Wu Y, Gossen J, Richards JS
  • Journal Title: Development vol. 135 (12) Pages: 2127-2137
  • Peer Reviewed
• [Journal Article] Hyaluronan fragments generated by sperm-secreted hyaluronidase stimula-te cytokines/chemokines production via TLR2 and TLR4 pathway in cumulus cells of ovulated COCs, which may enhance fertilization (2008)
  • Author(s): Shimada M, Yanai Y, Okazaki T, Noma N, Kawashima I, Mori T, Richards JS
  • Journal Title: Development vol. 135 (11) Pages: 2001-2011
  • Peer Reviewed
• [Journal Article] Hormone-induced expression of TACE/ADAM17 protease impacts porcine cumulus cell oocyte complex expansion and meiotic maturation via ligand activation of the EGF receptor (2008)
  • Author(s): Yamashita Y, Kawashima I, Yanai Y, Nishibori M, Richards JS, Shimada M
  • Journal Title: Endocrinology vol.148 Pages: 6164-6175
  • Peer Reviewed
• [Journal Article] The Immune-like Mechanisms in Ovulation (2008)
  • Author(s): Richards JS, Liu Z, Shimada M
  • Journal Title: Trend Endocrinol Metab vol. 19 (6) Pages: 191-196
  • Peer Reviewed
• [Journal Article] Hyaluronan fragments generated by sperm-secreted hyaluronidase stimulate cytokines/chemokines production via TLR2 and TLR4 pathway in cumulus cells of ovulated COCs, which may enhance fertilization. (2008)
  • Author(s): M. Shimada
  • Journal Title: Development 135・11 Pages: 2001-2011
  • Peer Reviewed
• [Journal Article] Somatic Expression of K-ras^<G12D> in Mouse Ovary Causes Defects of Follicle Development and Ovulation (2008)
  • Author(s): H. Fan
  • Journal Title: Development 135・12 Pages: 2127-2137
  • Peer Reviewed
• [Journal Article] Sequential exposure of porcine cumulus cells to FSH and/or LH is critical for appropriate expression of steroidogenic and ovulation related genes that impact oocvte maturation in vivo and in vitro (2008)
  • Author(s): I Kawashima
  • Journal Title: Reproduction 136・1 Pages: 9-21
  • Peer Reviewed
• [Journal Article] 卵子・卵丘細胞複合体-卵丘細胞による卵子成熟の制御機構- (2008)
  • Author(s): 島田昌之
  • Journal Title: 産婦人科診療 96・1 Pages: 18-24
• [Journal Article] Synaptosomal associated protein 25 (Snap25) gene expression is hormonally regulated during ovulation and is involved in cytokine/chemokine exocytosis from granulosa cells (2007)
  • Author(s): Shimada M, Yanai Y, Okazaki T, Yamashita Y, Sriraman Y, Wilson MC, Richards JS
  • Journal Title: Mol Endocrinol vol. 21(10) Pages: 2487-2502
  • Peer Reviewed
• [Journal Article] Synaptosonial-associated protein 25 gene expression is hormonally regulated during ovulation and is involved in cytokine/chemokine exocsrtosis from granulosa cells (2007)
  • Author(s): M. Shimada
  • Journal Title: Molecular Endocrinology 21・10 Pages: 2487-2502
  • Peer Reviewed
• [Journal Article] Hormone-induced expression of tunor necrosis factora-converting enzyme/a disintegrin and metalloprotease-17 imapacts porcine cumulus cell oocyte complex expansion and meiotic maturation via ligand activation of the epidermal growth factor receptor (2007)
  • Author(s): Y. Yamashita
  • Journal Title: Endocrinology 148 ・ 12 Pages: 6164-6175
  • Peer Reviewed
• [Journal Article] Assessment of human oocyte developmental competence by cumulus cell morphology and circulating hormone profile (2007)
  • Author(s): C.Sato, M.Shimada et al.7名中2番目
  • Journal Title: Reproductive BioMedicine Online 14 (1) Pages: 49-56
• [Journal Article] Involvement of Ca^<2+>-dependent proteasome in the degradation of both cyclin B1 and Mos during spontaneous activation of matured rat oocytes (2007)
  • Author(s): J.Ito, M.Shimada et al.4名中2番目
  • Journal Title: Theriogenology 67 Pages: 475-485
• [Journal Article] Induced expression of pattern recognition receptors (PRRs) in cumulus oocyte complexes (COCs) : Novel evidence for immune-like functions during ovulation (2006)
  • Author(s): Shimada M, Hernandez-Gonzalez I, Gonzalez-Robayna I, Richards JS
  • Journal Title: Mol Endocrinol. vol. 20 Pages: 3228-3239
  • Peer Reviewed
• [Journal Article] Paracrine and autocrine regulation of EGF-like factors in cumulus oocyte complexes (COCs) and granulosa cells : key roles for prostanglandin synthase 2 (Ptgs2) and progesterone receptor (Pgr) (2006)
  • Author(s): Shimada M, Hernandez-Gonzalez I, Gonzalez-Robayna I, Richards JS
  • Journal Title: Mol Endocrinol. Vol.20 (6) Pages: 1352-1365
  • Peer Reviewed
• [Journal Article] Paracrine and autocrine regulation of epidermal growth factor-like factors in cumulus oocyte complexes and granulosa cells : Key roles for prostaglandin synthase 2 and progesterone receptor (2006)
  • Author(s): M.Shimada et al.
  • Journal Title: Molecular Endocrinology 20(6) Pages: 1352-1365
• [Journal Article] Gene expression profiles of cumulus cell oocyte complexes during ovulation reveal cumulus cells express neuronal and immune-related genes : Does this expand their role in the ovulation process? (2006)
  • Author(s): I, Hernandez-Gonzalez, M. Shimada et al. 7名中3番目
  • Journal Title: Molecular Endocrinology 20(6) Pages: 1300-1321
• [Journal Article] Induced expression of pattern recognition receptors in cumulus oocyte complexes : Novel evidence for innate immune-like functions during ovulation (2006)
  • Author(s): M.Shimada et al.
  • Journal Title: Molecular Endocrinology 20(12)
• [Presentation] 顆粒膜細胞特異的ERK1/2 遺伝子欠損マウスを用いたLH サージによる卵胞内エストロジェン濃度低下が誘起する排卵機構の解析 (2009)
  • Author(s): 田畑慧・Fan HY・Richards JS.・下中麻奈美・野々口耕介・渡辺浩彦・森崇英・島田昌之
  • Organizer: 第50回日本哺乳動物卵子学会大会
  • Place of Presentation: 東京
  • Year and Date: 2009-05-08
• [Presentation] ブタ成熟卵子の発生能向上に果たすNeuregulin 1 の役割 (2009)
  • Author(s): 川島一公・田畑慧・野間紀孝・岡崎哲司・島田昌之
  • Organizer: 第110回日本畜産学会大会
  • Place of Presentation: 藤沢
  • Year and Date: 2009-03-28
• [Presentation] ブタ成熟卵子の発生能向上に果たすNeuregulin 1の役割 (2009)
  • Author(s): 川島一公
  • Organizer: 日本畜産学会
  • Place of Presentation: 藤沢市
  • Year and Date: 2009-03-27
• [Presentation] ERK1/2 系が顆粒層細胞の排卵期特異的な遺伝子発現を誘起する (2009)
  • Author(s): 下中麻奈美, 田畑慧, Fan HY, Richards JS, 島田昌之
  • Organizer: 第4回日本生殖再生医学会
  • Place of Presentation: 東京
  • Year and Date: 2009-03-15
• [Presentation] 排卵過程の顆粒層細胞におけるAmphiregulin (AREG)発現制御機構の解析 (2008)
  • Author(s): 下中麻奈美,Richards JS,島田昌之
  • Organizer: 第13回日本生殖内分泌学会大会
  • Place of Presentation: 大阪
  • Year and Date: 2008-11-30
• [Presentation] 排卵過程の顆粒層細胞におけるAmphireguhn (AREG)発現制御機構の解析 (2008)
  • Author(s): 下中麻奈美
  • Organizer: 日本生殖内分泌学会
  • Place of Presentation: 大阪市
  • Year and Date: 2008-11-29
• [Presentation] 卵丘細胞に発現するToll-like receptor(TLR)によるケモカイン分泌磯構の基礎的解明とヒト体外受精不成功症例におけるケモカイン類の網羅的解析 (2008)
  • Author(s): 島田昌之
  • Organizer: 日本受精着床学会
  • Place of Presentation: 福岡市
  • Year and Date: 2008-08-24
• [Presentation] Expression of synaptotagniin 1 (Syt1) is induced and facilitatcs secretion vubicle binding to the granulosa/cumulus cell plasma membrane protein SNAP 25 during ovulation in the mouse (2008)
  • Author(s): M. Shimada
  • Organizer: The Endocrine Society
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2008-06-04
• [Presentation] LSL/Kras<^G12/D> ; Cyp 19 Creマウスを用いたEGF like familyが誘起する卵子成熟機構の解析 (2008)
  • Author(s): 野間紀孝
  • Organizer: 日本哺乳動物卵子学会
  • Place of Presentation: 名古屋市
  • Year and Date: 2008-05-30
• [Presentation] Sequential exposure of porcine cumulus cells to FSH and LH is critical for appropriate expression of steroidogenic and ovulation related genes that impact oocyte maturation in vivo (2008)
  • Author(s): Shimada M, Kawashima I, Okazaki T, Yamashita Y
  • Organizer: in vitro 41th Annual Meeting of Society for the Study of Reproduction
  • Place of Presentation: Cona,Hawai,USA
  • Year and Date: 2008-05-25
• [Presentation] Sequential exposure of porcine cumulus cells to FSH and LH is critical for appropriate expression of steroidogenic and ovulation related genes that impact oocyte maturation in vivo and in vitro (2008)
  • Author(s): M. Shimada
  • Organizer: The Society for the Study of Reproduction
  • Place of Presentation: Kona, USA
  • Year and Date: 2008-05-24
• [Presentation] LSL/KrasG12/D ; Cyp19Cre マウスを用いたEGF like family が誘起する卵子成熟機構の解析 (2008)
  • Author(s): 野間紀孝・Fan HY・Richards JS・島田昌之
  • Organizer: 第49回日本哺乳動物卵子学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-05-13
• [Presentation] The role of Toll-like receptor 2 and 4 expressed on cumulus cells of ovulated COC_s during fertilization process (2007)
  • Author(s): Y. Yanai
  • Organizer: International Ovarian Conference
  • Place of Presentation: 箱根町
  • Year and Date: 2007-11-02
• [Presentation] 排卵過程の顆粒層細胞におけるSNAP25により制御されるホルモン分泌機構 (2007)
  • Author(s): 島田昌之
  • Organizer: 日本生殖内分泌学会
  • Place of Presentation: 東京都
  • Year and Date: 2007-10-29
• [Presentation] 排卵過程の顆粒層細胞に おけるSNAP25 により制御されるホル モン分泌機構 (2007)
  • Author(s): 島田昌之,柳内嘉在,西松恵子,Richards JS,西堀正英
  • Organizer: 第12回日本生殖内分泌学会大会
  • Place of Presentation: 東京
  • Year and Date: 2007-10-18
• [Presentation] 受精過程に分解されるヒアルロン酸 は,卵丘細胞のToll-like receptor を介してケモカインを分泌させ,精子の受精能獲得を誘起させる (2007)
  • Author(s): 島田昌之,柳内嘉在,岡崎哲司, Richards JS
  • Organizer: 第25回日本受精着床学会
  • Place of Presentation: 仙台
  • Year and Date: 2007-08-30
• [Presentation] 受精過程に分解されるヒアルロン酸は,卵丘細胞のToll-like receptorを介してケモカインを分泌させ,精子の受精能獲得を誘起させる (2007)
  • Author(s): 島田昌之
  • Organizer: 日本受精着床学会
  • Place of Presentation: 仙台市
  • Year and Date: 2007-08-29
• [Presentation] Activation of Toll-like receptors 2 and 4 on cumulus cells of ovulated cumulus oocyte complexes stimulates production of cytokines/chemokines that can induce sperm capacitation leading to successful fertilization (2007)
  • Author(s): Shimada M, Yanai Y, Okazaki T, Richards JS
  • Organizer: 40th Annual Meeting of Society for the Study of Reproduction
  • Place of Presentation: San Antonio, USA
  • Year and Date: 2007-07-26
• [Presentation] Activation of Toll-like receptors 2 and 4 on cumulus cells of ovulated cumulus oocyte complexes stimulates production of cytokines/cliemokines that can induce sperm capacitation leading to successful fertilization (2007)
  • Author(s): M. Shimada
  • Organizer: The Society for the Study of Reproduction
  • Place of Presentation: San Antonio, USA
  • Year and Date: 2007-07-20
• [Presentation] Expression of the murine synaptosome-associated protein 25 (Snap25) gene is required for cytokine exocvtosis from granulosa cells (2007)
  • Author(s): M. Shimada
  • Organizer: The Endocrine Society
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2007-06-02
• [Presentation] 卵丘細胞におけるADAM17発現変化とそのEGF like factor系を介した卵丘細胞の膨潤に果たす役割 (2007)
  • Author(s): 山下泰尚
  • Organizer: 日本哺乳動物卵子学会
  • Place of Presentation: 甲府市
  • Year and Date: 2007-05-30
• [Presentation] During ovulation pattern recognition receptors (PRRs) characteristic of immune cells are induced in cumulus oocyte complexes (COCs) to confer immune cell-like functions (2006)
  • Author(s): Shimada M, Hernandez-Gonzalez I, Gonzalez-Robanya I, Richards JS
  • Organizer: 39th Annual Meeting of Society for the Study of Reproduction
  • Place of Presentation: Omaha,USA
  • Year and Date: 2006-07-31
• [Remarks]
  • URL: http://home.hiroshima-u.ac.jp/seisyoku/framepage%20shimada.html