2002 Fiscal Year Annual Research Report

哺乳類卵胞の選択的死滅制御機構とその人為支配による潜在的卵巣卵の利用

Research Project

Project/Area Number	13GS0008
Research Institution	Kyoto University
Principal Investigator	眞鍋昇京都大学, 農学研究科, 助教授 (80243070)
Co-Investigator(Kenkyū-buntansha)	杉本実紀京都大学, 農学研究科, 助手 (20243074) 宮野隆神戸大学, 農学部, 教授 (80200195) 酒巻和弘京都大学, 生命科学研究科, 助教授 (20271017) 中山瑞穂京都大学, 農学研究科・日本学術振興会, 特別研究員(PD)
Keywords	哺乳類 / 卵巣 / 卵胞 / 選択的死滅 / アポトーシス / 細胞死受容体 / カスパーゼ / 異種移植
Research Abstract	脊椎動物の生殖戦略は多様である。哺乳類は、硬骨魚類のサケのように一生に一度だけ全卵子を排卵Lて数千から数億の仔を生み、その仔の中で優れたものが生き残る戦略と異なり、性周期毎に1から10個の卵母細胞を成熟・排卵し、極わずかの仔を産み、その仔を大切に育くむ戦略をとって繁栄してきた。哺乳類卵巣には胎児期に減数分裂ディプロテン期で休止した卵母細胞が5〜100万個含まれる。性成熟後は性周期毎に卵母細胞は卵胞ともに発育・成熟する。この時卵巣内では最終的に排卵にいたる卵子の100倍以上の卵胞が発達を開始するが、発育・成熟の過程で99%以上の卵母細胞が選択的に死滅し、1%未満の二次卵母細胞のみが排卵に至る。卵胞の選択的死滅は、より優秀で強靭な子孫を残す戦略として重要であるが、これの分子制御機構は未解明である。本研究は、哺乳類において卵胞の選択的死滅を制御している分子機構を解明し、これをもとに細胞死を制御している遺伝子の発現をin vivo制御することで卵胞の発達を人為的に支配し、卵巣内に潜在する卵母細胞の有効利用を実現することを目指している。今年度は、新規な細胞死受容体を認識するユニークなモノクロナル抗体を用いて、囮(デコイ)受容体を発見・同定した。卵巣で発現していることが知られている細胞死受容体であるFasの細胞内シグナル伝達系を担うカスパーゼ系の細胞内シグナル伝達を蛍光エネルギー移動(fluorescence resonance transfer : FRET)法にてリアルタイムにin situ解析できる新規な手法を開発した。また多面的機能をもつinterleukin-6が卵胞選抜に重要に関わっていることを示唆する知見を得た。併行して、ノックアウトしたマウス、免疫不全マウスの腎に移植(異種移植)したウシ、ブタなどの大型哺乳類の未成熟な卵胞を用いて、アポトーシスシグナル伝達系の分子制御機構の解析を進めた。

Research Products
(24 results)

All Other

All Publications (24 results)

[Publications] Mizuho Nakayama, Noboru Manabe, Naoko Inoue, Toshikatsu Matsui, Hajime Miyamoto: "Changes in the expression of tumor necrosis factor (TNF)a, TNFa Receptor (TNFR) 2 and TNFR-associated factor2 in granulosa cells during atresia in pig ovaries"Biology of Reproduction. 68・2. 530-535 (2003)
[Publications] Uchio K, Tuchweber B, Manabe Noboru, Gabbiani G, Rosenbaum J, Desmouliere A.: "Cellular retinol-binding protein-1 expression and modulation during in vivo and in vitro myofibroblastic differentiation of rat hepatic stellate cells and portal fibroblasts"Laboratory Investigation. 82・4. 619-628 (2002)
[Publications] Chiemi Tajima, Noboru Manabe, Mizuho Nakayama, Naoko Inoue, Toshikatsu Matsui, Eiichi Hondo, Hajime Miyamoto: "Monoclonal antibody recognizes follicular granulosa cell antigens in porcine ovaries"Journal of Reproduction and Devevelopment. 48・4. 567-572 (2002)
[Publications] Satoshi Imanishi, Noboru Manabe, Takako Tanaka, Reika Okamoto, Maki Morita, Miki Sugimoto, Hajime Miyamoto: "mRNA of GPCR5B/Raig2, a novel orphan receptor, expresses in murine placentae"Journal of Reproduction and Devevelopment. 48・4. 627-632 (2002)
[Publications] Noboru Manabe: "Molecular mechanism of follicle selection in mammalian ovaries"Journal of Laboratory Animals (Kansai). 23・1. 71-78 (2002)
[Publications] Noboru Manabe, Miki Sugimoto, Hajime Miyamoto: "In vivo noninvasive nuclear magnetic resonance (NMR) technique for assessment of teratogenicity induced by chemicals"Chemical Engineering. 47・2. 110-114 (2002)
[Publications] Satoko Wada, Noboru Manabe, Naoko Inoue, Mizuho Nakayama, Toshikatsu Matsui, Hajime Miyamoto: "TRAIL-decoy receptor-1 disappears in granulosa cells of atretic follicles in porcine ovaries"Journal of Reproduction and Devevelopment. 48・1. 167-173 (2002)
[Publications] Satoko Wada, Noboru Manabe, Naoko Inoue, Mizuho Nakayaina, Toshikatsu Matsui, Hajime Miyamoto: "TRADD is involved in apoptosis induction in granulosa cells during atresia in pig ovaries"Journal of Reproduction and Devevelopment. 48・1. 175-181 (2002)
[Publications] Hideki Tonomura H, Miyake T, Taniguchi Y, Manabe Noboru, Kose H, Matsumoto K, Yamada T, Sasaki Y.: "Detection of quantitative trait locus for rat model useful for genetic analysis of intramascular fat accumulation using the OLETF rat"The Journal of Veterinary Medical Science. 64・1. 45-50 (2002)
[Publications] Satoko Wada, Noboru Manabe, Mizuho Nakayama, Naoko Inoue, Toshikatsu Matsui, Hajime Miyamoto: "TRAIL-decoy receptor-1 plays inhibitory role in apoptosis of granulosa cells from pig ovarian follicules"The Journal of Veterinary Medical Science. 64・5. 435-439 (2002)
[Publications] Miki Sugimoto, Noboru Manabe, Maki Morita, Takako Tanaka, Reika Okamoto, Satoshi Imanishi, Hajime Miyamoto: "NMR microscopic observation of mouse embryo malformations induced by maternal administration of retinoic acid"The Journal of Veterinary Medical Science. 64・5. 427-433 (2002)
[Publications] Miki Sugimoto, Noboru Manabe, Hajime Miyamoto: "Cryopreservation techniques for ovarian tissues"Hormone Frontier in Gynecology. 9・1. 135-140 (2002)
[Publications] Noboru Manabe, Naoko Lnoue, Toshikatsu Matsui, Shinsuke Nakagawa, Akihisa Maeda, Takashi Miyano, Kazuhiro Sakamaki, Miki Sugimoto, Hajime: "Animal Frontier Science (Sato E, Miyamoto H, Manabe Noboru eds.), Regulatory mechanisms of follicle selection in mammalian ovaries. PP. 117-132"Hokuto Publication Company, Kyoto, Japan. 363 (2003)
[Publications] Noboru Manabe, Naoko Inoue, Toshikatsu Matsui, Shinsuke Nakagawa, Akihisa Maeda, Takashi Miyano, Kazuhiro Sakamaki, Miki Sugimoto, Hajime Miyamoto: "Animal Frontier Science (Sato E, Miyamoto H, Manabe Noboru eds.), Tumor necrosis factor-related apoptosis-inducing ligand and its receptors play crucial roles in apoptosis of granulosa cells during follicular atresia in pig ovaries. PP. 133-142"Hokuto Publication Company, Kyoto, Japan. 363 (2003)
[Publications] Mizuho Nakayama, Noboru Manabe, Naoko Inoue, Toshikatsu Matsui, Shinsuke Nakagawa, Akihisa Maeda, Hajime Miyamoto Sakamaki, Miki Sugimoto, Hajime Miyamoto: "Animal Frontier Science (Sato E, Miyamoto H, Manabe Noboru eds.), Tumor necrosis factor-α acts as a survival factor in granulosa cells during follicular selection in porcine ovaries. PP. 143-149"Hokuto Publication Company, Kyoto, Japan. 363 (2003)
[Publications] Naoko Inoue, Noboru Manabe, Toshikatsu Matsui, Shinsuke Nakagawa, Akihisa Maeda, Hajime Miyamoto: "Animal Frontier Science (Sato E, Miyamoto H, Manabe Noboru eds.), Roles of Fas-ligand and TRAIL systems in granulosa cell apoptosis during follicular atresia in porcine ovaries. PP. 151-156"Hokuto Publication Company, Kyoto, Japan. 363 (2003)
[Publications] Toshikatu Matsui, Noboru Manabe, Yasufumi Goto, Naoko Inoue, Shinsuke Nakagawa, Akihisa Maeda, Susumu Nishihara, Hajime Miyamoto: "Animal Frontier Science (Sato E, Miyamoto H, Manabe Noboru eds.), Role of the mitochondria-dependent pathway in granulosa cell apoptosis during follicular atresia in pig ovaries. PP. 157-163"Hokuto Publication Company, Kyoto, Japan. 363 (2003)
[Publications] Yamaguchi-Yamada M, Noboru Manabe, Uchio-Yamada K, Akashi N, Gotoh Y, Nagao M, Yamamoto Y, Ogura A, Miyamoto H.: "Animal Frontier Science (Sato E, Miyamoto H, Manabe Noboru eds.), Anemia associated with renal failure in the ICR-derived glomerulonephritis (ICGN) mice. PP. 281-285"Hokuto Publication Company, Kyoto, Japan. 363 (2003)
[Publications] Minako Kiso, Noboru Manabe, Kohji Komatsu, Munetake Shimabe, Hajime Miyamoto: "Animal Frontier Science (Sato E, Miyamoto H, Manabe Noboru eds.), Abnormal structural luteolysis in ovaries of the senescence accelerated mouse (SAM) : expression of Fas mediated apoptosis signal in luteal bodies. PP. 287-294"Hokuto Publication Company, Kyoto, Japan. 363 (2003)
[Publications] Noboru Manabe, Kozue Yamada-Uchio, Misuzu Yamada-Yamaguchi, Yasufumi Gotoh, Toshiharu Mori, Chinatsu Sakata, Yoshihiro Furuya, Hajime Miyamoto: "Animal Frontier Science (Sato E, Miyamoto H, Manabe Noboru eds.), Histochemical technique quantitatively estimates the physiological and pathological properties. PP. 303-309"Hokuto Publication Company, Kyoto, Japan. 363 (2003)
[Publications] Maki Morita, Miki Sugimoto, Noboru Manabe, Hajime Miyamoto: "Animal Frontier Science (Sato E, Miyamoto H, Manabe Noboru eds.), Morphological alterations in mammalian reproductive organ induced by exposure to diethylstilbestrol (DES). PP. 319-323"Hokuto Publication Company, Kyoto, Japan. 363 (2003)
[Publications] Miki SUGIMOTO, Noboru MANABE, Maki MORITA, Hajime MIYAMOTO: "Animal Frontier Science (Sato E, Miyamoto H, Manabe Noboru eds.), Utilization of magnetic resonance microscope for studies in reproductive toxicology. PP. 325-330"Hokuto Publication Company, Kyoto, Japan. 363 (2003)
[Publications] Noboru Manabe, Yasuyoshi Azuma, Miki Sugimoto, Kei-Ichi Sezaki, Mineko Iwahori, Satoshi Imanishi, Hanako Nishizawa, Takako Tanaka, Maki Morita, Hajime Miyamoto: "Animal Frontier Science (Sato E, Miyamoto H, Manabe Noboru eds.), In vivo and real time estimation of energy metabolism by ^<31>p-nuclear magnetic resonance. PP. 339-347"Hokuto Publication Company, Kyoto, Japan. 363 (2003)
[Publications] Morikawa Masahiro, Wakoto Matsuyama, Yuko Kawamoto, Miki Sugimoto, Maki Morita, Aki Nakayama, Noboru Manabe, Minoru Yoneda, Shinsuke Morisawa: "Environmental Toxicity Evaluation and Risk Management Vol. 1 (Morisawa S eds.), Dynamic performance of bisphenol-A (BPA) in pregnant mouse and physiologically-based pharmacokinetic model development. PP. 60-74"The Environment Risk Management Group of The JSPS-VCC Program on Environmental Science, Engineering and Ethics 2000-2009. Kyoto, Japan. 159 (2002)

2002 Fiscal Year Annual Research Report

哺乳類卵胞の選択的死滅制御機構とその人為支配による潜在的卵巣卵の利用

Principal Investigator

眞鍋 昇 京都大学, 農学研究科, 助教授 (80243070)

Research Products

[Publications] Chiemi Tajima, Noboru Manabe, Mizuho Nakayama, Naoko Inoue, Toshikatsu Matsui, Eiichi Hondo, Hajime Miyamoto: "Monoclonal antibody recognizes follicular granulosa cell antigens in porcine ovaries"Journal of Reproduction and Devevelopment. 48・4. 567-572 (2002)

[Publications] Satoshi Imanishi, Noboru Manabe, Takako Tanaka, Reika Okamoto, Maki Morita, Miki Sugimoto, Hajime Miyamoto: "mRNA of GPCR5B/Raig2, a novel orphan receptor, expresses in murine placentae"Journal of Reproduction and Devevelopment. 48・4. 627-632 (2002)

[Publications] Noboru Manabe: "Molecular mechanism of follicle selection in mammalian ovaries"Journal of Laboratory Animals (Kansai). 23・1. 71-78 (2002)

[Publications] Noboru Manabe, Miki Sugimoto, Hajime Miyamoto: "In vivo noninvasive nuclear magnetic resonance (NMR) technique for assessment of teratogenicity induced by chemicals"Chemical Engineering. 47・2. 110-114 (2002)

[Publications] Satoko Wada, Noboru Manabe, Naoko Inoue, Mizuho Nakayama, Toshikatsu Matsui, Hajime Miyamoto: "TRAIL-decoy receptor-1 disappears in granulosa cells of atretic follicles in porcine ovaries"Journal of Reproduction and Devevelopment. 48・1. 167-173 (2002)

[Publications] Satoko Wada, Noboru Manabe, Naoko Inoue, Mizuho Nakayaina, Toshikatsu Matsui, Hajime Miyamoto: "TRADD is involved in apoptosis induction in granulosa cells during atresia in pig ovaries"Journal of Reproduction and Devevelopment. 48・1. 175-181 (2002)

[Publications] Satoko Wada, Noboru Manabe, Mizuho Nakayama, Naoko Inoue, Toshikatsu Matsui, Hajime Miyamoto: "TRAIL-decoy receptor-1 plays inhibitory role in apoptosis of granulosa cells from pig ovarian follicules"The Journal of Veterinary Medical Science. 64・5. 435-439 (2002)

[Publications] Miki Sugimoto, Noboru Manabe, Maki Morita, Takako Tanaka, Reika Okamoto, Satoshi Imanishi, Hajime Miyamoto: "NMR microscopic observation of mouse embryo malformations induced by maternal administration of retinoic acid"The Journal of Veterinary Medical Science. 64・5. 427-433 (2002)

[Publications] Miki Sugimoto, Noboru Manabe, Hajime Miyamoto: "Cryopreservation techniques for ovarian tissues"Hormone Frontier in Gynecology. 9・1. 135-140 (2002)

[Publications] Miki SUGIMOTO, Noboru MANABE, Maki MORITA, Hajime MIYAMOTO: "Animal Frontier Science (Sato E, Miyamoto H, Manabe Noboru eds.), Utilization of magnetic resonance microscope for studies in reproductive toxicology. PP. 325-330"Hokuto Publication Company, Kyoto, Japan. 363 (2003)

眞鍋昇京都大学, 農学研究科, 助教授 (80243070)