2002 Fiscal Year Annual Research Report

生体NMRイメージング法による生殖毒性のリアルタイム評価法の創出

Research Project

Project/Area Number	14360167
Research Institution	Kyoto University
Principal Investigator	宮本元京都大学, 農学研究科, 教授 (00026618)
Co-Investigator(Kenkyū-buntansha)	杉本実紀京都大学, 農学研究科, 助手 (20243074) 眞鍋昇京都大学, 農学研究科, 助教授 (80243070)
Keywords	外因性内分泌撹乱物質 / 核磁気共鳴イメージング / 三次元形態解析 / 哺乳類 / 胎仔 / オーファン受容体 / 受容体ノックアウト / リアルタイム解析
Research Abstract	人類は19世紀に化学合成という新しい技術を獲得し、農薬、食品添加物などの多くの化合物を創出して食料の増産と繁栄を実現してきた。ところがこれらの化合物の多くが哺乳類の様々な内分泌系に作用してその機能を撹乱させてしまうことが20世紀末になって判明してきた。特に一群の化合物は生殖機能に機能異常を誘発(外因性内分泌撹乱物質)し、人類の生存を脅かしている。既知の内分泌撹乱物質への対応は言うまでもなく、それら以外の環境系に存在する様々な化合物による生殖毒性を鋭敏かつ速やかに検出・評価する技術を確立することは、21世紀の科学が克服しなくてはならない重要な研究課題である。生殖生理学に関わる新技術開発や生殖子の選抜機構研究を進めてきた申請者らは、本年度は生体核磁気共鳴装置(NMR)を用いて胎仔形態形成異常の非破壊的・リアルタイム評価法の開発を進めた。この新手法は、従来用いられてきた手法とは異なる新規な原理に基づき、リアルタイムかつ非侵襲的に生殖毒性を観測・評価できる技術システムの構築を実現するものである。具体的には、麻酔下の妊娠マウスを生体NMRの特性プローブベッドに保定し、胎児におけるNMRシグナルを部位特異的にリアルタイムに検出できる測定アプリケーション(コンピュータープログラム)の作成と最適測定条件の決定を行った。加えて、ゲノムDNAの構造解析、エネルギー産生機能解析、トランスミッター動態の解析、細胞ホメオスターシスの解析、を行うための基盤となる技術開発を進めた。併行して、最先端の哺乳類細胞における遺伝子工学的手法を駆使して、人為約に構造変異(アミノ酸の一次構造の変異)を誘導したホルモン受容体を作成して、化合物/受容体の相互的結合特性をin vitro的に観測して分子構造学的に毒性を予測する手法の開発を進めた。

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 factor 2 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 libroblasts"Laboratory Investigation. 82・4. 619-628 (2002)
[Publications] Chiemi Tajima, Noboru Manabe, Mizuho Nakayama, Naoko Inoue, Toshikatsu Matsui, Eiichi Hondo, Hajime Miyamoto Hajime: "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 Nakayama, 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. 178-181 (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] 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] Toshikatsu Matsui, Noboru Manabe, Yasufumi Goto, Naoko Inoue, Shinsuke Nadagawa, 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] Noboru Manabe, Naoko Inoue, 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 Nadagawa, 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] 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

生体NMRイメージング法による生殖毒性のリアルタイム評価法の創出

Principal Investigator

宮本 元 京都大学, 農学研究科, 教授 (00026618)

Research Products

[Publications] Chiemi Tajima, Noboru Manabe, Mizuho Nakayama, Naoko Inoue, Toshikatsu Matsui, Eiichi Hondo, Hajime Miyamoto Hajime: "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 Nakayama, 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. 178-181 (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)

宮本元京都大学, 農学研究科, 教授 (00026618)