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

• 研究課題/領域番号: 13GS0008
• 研究種目: 学術創成研究費
• 配分区分: 補助金
• 研究機関: 東京大学 (2004-2005); 京都大学 (2001-2003)
• 研究代表者: 眞鍋 昇 東京大学, 大学院農学生命科学研究科, 教授 (80243070)
• 研究分担者: 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) ; 若山 照彦 理化学研究所, 神戸研究所・発生再生科学総合研究センター, チームリーダー(研究職) (40360672) ; 杉本 実紀 京都大学, 農学研究科, 助手 (20243074) ; 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)
• 研究期間 (年度): 2001 – 2005
• 研究課題ステータス: 完了 (2005年度)
• 配分額: 347,750千円 (直接経費: 288,200千円、間接経費: 59,550千円); 2005年度: 83,850千円 (直接経費: 64,500千円、間接経費: 19,350千円); 2004年度: 84,500千円 (直接経費: 65,000千円、間接経費: 19,500千円); 2003年度: 89,700千円 (直接経費: 69,000千円、間接経費: 20,700千円); 2002年度: 89,700千円 (直接経費: 89,700千円)
• キーワード: 哺乳類 / 卵巣 / 卵胞 / 選択的死滅 / アポトーシス / 細胞死受容体 / 細胞内シグナル伝達阻害因子 / 異種移植 / カスパーゼ

研究概要

脊椎動物は多様な生殖戦略をもつ。魚類の多くは数万〜数億のなかで幸運で優れた仔だけが生き残る。逆に、哺乳類は性周期毎に1〜10個の卵母細胞を排卵し、極わずかの仔を産み、それを大切に育てる。成熟した哺乳類卵巣には、胎児期に減数分裂の途中・ディプロテン期で休止した5〜100万個の卵母細胞が含まれ、これが性周期毎に発育・成熟して排卵に至る。この過程で、最終的に排卵にいたるものの100倍以上の卵胞が発達を開始し、99%以上が選択的に死滅する。この卵胞の選択的死滅は優秀で強靭な子孫を残す戦略として重要であるが、これを調節している分子制御機構は未解明である。本研究は、哺乳類卵巣において繰返される卵胞の選択的死滅を支配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発育を人為的に支配しようとするものである。この新技術で、食肉処理場で捨てられる卵巣内の卵母細胞の有効利用を実現しようとしている。今年度は実証的研究に注力した。卵胞顆粒層細胞に特異的に発現している新規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デコイ受容体を同定し、その発現動態を明らかとした。さらに細胞死受容体を介する細胞内アポトーシスシグナル伝達系を担うカスパーゼ系を阻害するcFLIPを見いだして遺伝子とアミノ酸配列を決定した。これの発現を腫瘍壊死因子α調節し、その制御に多面的機能をもつinterleukin-6が重要に関わっていることを示唆した。併行して、大型家畜の未成熟な卵胞を含む卵巣片を免疫不全マウス腎漿膜嚢に異種移植し、in vivo遺伝子導入とRNA発現阻止(iRNA)にて人為的に制御できるシステムを開発した。

研究成果

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• [雑誌論文] CFLIP regulates granulose cell apoptosis during follicular atresia in porcine ovaries.(abstrqact) (2005)
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• [雑誌論文] Apoptosis is regulated by soluble Fas during luteolysis in Iuteal cells of mouse ovaries.(abstrqact) (2005)
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• [雑誌論文] Connexin-43 has relation to regulation of granulosa cell apoptosis during atresia in pig ovarian follicules. (abstrqact) (2005)
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  • NAID: 120001460015
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  • NAID: 10027322921
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  • NAID: 10026620927
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• [雑誌論文] Production of offspring from one-day-old oocytes stored at room temperature. (2004)
  • 著者名/発表者名: Wakayama, S., Thuan, N.V., Kishigami, S., Ohta, H., Mizutani, E., Hikichi, T., Miyake, M., Wakayama, T.
  • 雑誌名: Journal of Reproduction and Development 50・6 ページ: 627-637
  • NAID: 10027323645
• [雑誌論文] The porcine (Sus scrofa) cellular Flice-like inhibitory protein (cFLIP) : molecular cloning and comparison with the human and murine cFLIP. (2004)
  • 著者名/発表者名: Yasufumi Goto, Fuko Matsuda, Toshikatsu Matsui, Akihisa Maeda, Naoko Inoue, Noboru Manabe
  • 雑誌名: Journal of Reproduction and Development 50・6 ページ: 549-555
  • NAID: 10027323381
• [雑誌論文] Expression of epidermal growth factor receptor (EGF-R)-, vascular endothelial growth factor receptor (VEGF-R) and fibroblast growth factor receptor (FGF-R) systems in porcine oviduct and endometrium during the time of implantation. (2004)
  • 著者名/発表者名: Karin Wollenhaupt, Harald Welter, Ralf Einspanier, Noboru Manabe, Klaus-Peter Brussow
  • 雑誌名: Journal of Reproduction and Development 50・2 ページ: 269-278
  • NAID: 10027322327
• [雑誌論文] differential transcriptional and translational regulations of calbindin-D9k by steroid hormones and their receptors in the uterus of immature mice. (2004)
  • 著者名/発表者名: Beum-Soo An, Kyung-Chul Choi, Eui-Ju Hong, Yong-Woo Jung, Noboru Manabe, Eui-Bae Jeung
  • 雑誌名: Journal of Reproduction and Development 50・4 ページ: 445-453
• [雑誌論文] Full-term development of offspring using round spermatids produced ectopically from fetal male germ cells. (2004)
  • 著者名/発表者名: Ohta, H., Wakayama, T.
  • 雑誌名: Journal of Reproduction and Development 50・5 ページ: 429-437
  • NAID: 10027322895
• [雑誌論文] Changes in the localization of type I, III and IV collagen mRNAs in the kidneys of hereditary nephritic (ICGN) mice with renal fibrosis. (2004)
  • 著者名/発表者名: Kozue Uchio-Yamada, Noboru Manabe, Misuzu Yamaguchi-Yamada, Yasufumi Goto, Yoshie Yamamoto, Atsuo Ogura, Hajime Miyamoto
  • 雑誌名: The Journal of Veterinary Medical Science 66・1 ページ: 123-128
  • NAID: 110003886367
• [雑誌論文] Anemia with chromic renal disorder and disrupted metabolism of erythropoietin in ICR-derived glomerulonephritis (ICGN) mice. (2004)
  • 著者名/発表者名: Misuzu Yamaguchi-Yamada, Noboru Manabe, Kozue Uchio-Yamada, Naotsugu Akashi, Yasufumi Gotoh, Youhei Miyamoto, Masaya Nagao, Yoshie Yamamoto, Atsuo Ogura, Hajime Miyamoto
  • 雑誌名: The Journal of Veterinary Medical Science 66・3 ページ: 423-431
• [雑誌論文] Improvement of anemia associated with chronic renal failure by recombinant human erythropoietin treatment in ICR-derived glomerulonephritis (ICGN) mice. (2004)
  • 著者名/発表者名: Misuzu Yamaguchi-Yamada, Noboru Manabe, Yshufumi Goto, Sayuri Anann, Keiko Miyamoto, Youhei Miyamoto, Masaya Nagao, Yoshie Yamamoto, Atsuo Ogura
  • 雑誌名: The Journal of Veterinary Medical Science 66・7 ページ: 883-886
  • NAID: 110003960155
• [雑誌論文] Myofibroblastic differentiation in tubulointerstitial cells is provoked by augmented cytoplasmic Smad4 protein in hereditary nephrotic ICGN mice with chronic renal fibrosis. (2004)
  • 著者名/発表者名: Ysufumi Goto, Noboru Manabe, Kozue Uchio, Misuzu Yamaguchi-Yamada, Naoko Inoue, Atsuo Ogura
  • 雑誌名: Cell and Tissue Research 315・1 ページ: 209-221
• [雑誌論文] Different molecular mechanisms underlie placental overgrowth phenotypes caused by interspecies hybridization, cloning, and Esx1 mutation. (2004)
  • 著者名/発表者名: Singh, U., Fohn, L.E., Wakayama, T., Ohgane, J., Steinhoff, C., Lipkowitz, B., Schulz, R., Orth, A., Ropers, H.H., Behringer, R.R., Tanaka, S., Shiota, K., Yanagimachi, R., Nuber, U.A., Fundele, R.
  • 雑誌名: Developmental Dynamics 230・1 ページ: 149-164
• [雑誌論文] Skewed X-inactivation in cloned mice. (2004)
  • 著者名/発表者名: Senda, S., Wakayama, T., Yamazaki, Y., Ohgane, J., Hattori, N., Tanaka, S., Yanagimachi, R., Shiota, K.
  • 雑誌名: Biochemistry Biophysics Research Communication 321・1 ページ: 38-44
• [雑誌論文] Regeneration of the infarcted heart with stem cells derived by nuclear transplantation. (2004)
  • 著者名/発表者名: Lanza, R., Moore, M.A., Wakayama, T., Perry, A.C., Shieh, J.H., Hendrikx, J., Leri, A., Chimenti, S., Monsen, A., Nurzynska, D., West., M.D., Kajstura, J., Anversa, P.
  • 雑誌名: Circlation Research 94・2 ページ: 820-827
• [雑誌論文] The histone deacetylase inhibitor tricostatin A induces retrogressive chromatin decondensation in the germinal vesicle of fully grown porcine oocytes. (2004)
  • 著者名/発表者名: Yuji Hirao, Naoki Takenouchi, Manabu Shimizu, Kosuke Iga, Takashi Miyano, Takashi Nagai
  • 雑誌名: Journal of Mammalian Ova Research 21・3 ページ: 110-117
• [雑誌論文] Activation and development of pig oocytes after microinjection of crude sperm extract. (2004)
  • 著者名/発表者名: Konosuke Okada, Takashi Miyano, Masashi Miyake
  • 雑誌名: Journal of Mammalian Ova Research 21・3 ページ: 134-140
  • NAID: 10014108967
• [雑誌論文] Xenografting of bovine secondary follicles into male and female SCID mice. (2004)
  • 著者名/発表者名: Shoichiro Senbon, Atsushi Ota, Masao Tachibana, Takashi Miyano
  • 雑誌名: Journal of Mammalian Ova Research 21・3 ページ: 157-161
  • NAID: 10014109074
• [雑誌論文] Regulation of endothelial cell death and its role in angiogenesis and vascular regression. (2004)
  • 著者名/発表者名: Kazuhiro Sakamaki
  • 雑誌名: Current Neurovascular Research 1・1 ページ: 305-315
• [雑誌論文] Age-related thymic involution is mediated by Fas on thymic epithelial cells. (2004)
  • 著者名/発表者名: Nobuyuki Yajima, Kazuhiro Sakamaki, Shin Yonehara
  • 雑誌名: International Immunology 16・5 ページ: 1027-1035
  • NAID: 10013292015
• [雑誌論文] The Sa113 locus is an epigenetic hotspot of aberrant DNA methylation associated with placentomegaly of cloned mice. (2004)
  • 著者名/発表者名: Ohgane, J., wakayama, T., Senda, S., Yamazaki, Y., Inoue, K., Ogura, A., Marh, J., Tanaka, S., Yanagimachi, R.Shiota, K.
  • 雑誌名: Genes Cells 9・1 ページ: 253-260
• [図書] Gamete Biology-Emerging Frontiers in Fertility and Contraceptive Development : Oocyte growth and acquisition of meiotic competence. (2006)
  • 著者名/発表者名: Miyano T, Manabe N.
  • 総ページ数: 312
  • 出版者: Nottinghm University Press
• [図書] Endocrine Disrupting Chemicals : Efect of various phtalates on the induction of Calbindin-D9k as an estrogen-like chemical in in vitro ans in vivo models. (2005)
  • 著者名/発表者名: Eui-Ju Hong, Youn-Kyu Ji, Kyung-Chul Choi, Noboru Manabe, Eui-Bae Jeung
  • 総ページ数: 482
  • 出版者: The Endocrine Society
• [図書] ウシの解剖・消化器系 (2005)
  • 著者名/発表者名: 眞鍋 昇
  • 総ページ数: 138
  • 出版者: チクサン出版株式会社
• [図書] 犬の繁殖(Dog Breeding) (2005)
  • 著者名/発表者名: 眞鍋 昇, 佐籐英明, 永村武美
  • 総ページ数: 338
  • 出版者: 株式会社インターズー
• [図書] 卵子形成・成熟および排卵の機能 : 生命の誕生に向けて (2005)
  • 著者名/発表者名: 宮野 隆
  • 総ページ数: 482
  • 出版者: 近代出版株式会社・日本哺乳動物卵子学会
• [図書] The Ovary (2nd edition) Chapter 21 : Follicle selection in mammalian ovaries : Regulatory mechanisms of granulosa cell apoptosis during follicular atresia.(Leung PCR, Adashi E eds)(pp 369-385) (2004)
  • 著者名/発表者名: Noboru Manabe, Naoko Inoue, Takashi Miyano, Kazuhiro Sakamaki, Miki Sugimoto, Hajime Miyamoto
  • 総ページ数: 664
  • 出版者: Academic Press/Elsevier, New York, USA
• [図書] Abnormal accumulation of corpora lutes in ovaries of the senescence accelerated mouse prone (SAMP). The Senescence-Accelerated Mouse (SAM) : An Animal Model of Senescence (Yasuyuki Nomura, Toshio Takeda, Yasunobu Okuma eds)(pp O79-785) (2004)
  • 著者名/発表者名: Noboru Manabe, Minako Kiso, Munetake Shimabe, Nami Nakai-Sugimoto, Hajime Miyamoto
  • 総ページ数: 448
  • 出版者: Elsevier Science Publishers B.V., Amsterdam, The Nederland
• [図書] Expression of matrix metalloproteinase (MMP) and tissue inhibitor of MMP in ovaries of senescence accelerated mice. The Senescence-Accelerated Mouse (SAM) : An Animal Model of Senescence (Yasuyuki Nomura, Toshio Takeda, Yasunobu Okuma eds)(pp 229-232) (2004)
  • 著者名/発表者名: Munetake Shimabe, Minako Kiso, Kohji Komatsu, Noboru Manabe, Hajime Miyamoto
  • 総ページ数: 448
  • 出版者: Elsevier Science Publishers B.V., Amsterdam, The Nederland
• [図書] Expression of prolactin receptor mRNA in ovaries of senescence accelerated mice. The Senescence-Accelerated Mouse (SAM) : An Animal Model of Senescence (Yasuyuki Nomura, Toshio Takeda, Yasunobu Okuma eds)(pp 233-236) (2004)
  • 著者名/発表者名: Minako Kiso, Munetake Shimabe, Kohji Komatsu, Noboru Manabe, Hajime Miyamoto
  • 総ページ数: 448
  • 出版者: Elsevier Science Publishers B.Y., Amsterdam, The Nederland
• [文献書誌] 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)
• [文献書誌] Kohji Komatsu, Noboru Manabe, Minako Kiso, Munetake Shimabe, Hajime Miyamoto: "Changes in localization of immune cells and cytokines in corpora lutea during luteolysis in murine ovaries."Journal of Experimental Zoology. 296(1). 152-159 (2003)
• [文献書誌] Kohji Komatsu, Noboru Manabe, Minako Kiso, Munetake Shimabe, Hajime Miyamoto: "Soluble Fas (FasB) regulates luteal cell apoptosis during luteolysis in murine ovaries."Molecular Reproduction and Development. 65. 345-352 (2003)
• [文献書誌] Toshikatsu Matsui, Noboru Manabe, Yasufumi Goto, Mizuho Nakayama, Naoko Inoue, Susumu Nishihara, Hajime Miyamoto: "Changes in the expression and activity of caspase-9 and Apafl in granulosa cells during follicular atresia in pig ovaries."Reproduction. 126. 113-120 (2003)
• [文献書誌] Istvan Egerszegi, Falk Schneider, Jozsef Ratky, Ferenc Soos, Laszlo Solti, Noboru Manabe, Klaus-Peter Brussow: "Comparison of luteinizing hormone and steroid hormone secretion during the peri-and post-ovulatory periods in mangalica and landrace gilts."Journal of Reproduction and Development. 49(4). 291-296 (2003)
• [文献書誌] Naoko Inoue, Noboru Manabe, Toshikatsu Matsui, Akihisa Maeda, Shynsuke Nakagawa, Satoko Wada, Hajime Miyamoto: "roles of tumor necrosis factor-related apoptosis-inducing ligand signaling pathway in granulosa cell apoptosis during atresia in pig ovaries."Journal of Reproduction and Devevelopment. 49(4). 313-321 (2003)
• [文献書誌] Satoshi Imanishi, Noboru Manabe, Hanako Nishizawa, Maki Morita, Miki Sugimoto, Mineko Iwahori, Hajime Miyamoto: "Effects of oral exposure of bisphenol A on mRNA expression of nuclear receptors in murine placentae assessed by DNA microarray."Journal of Reproduction and Devevelopment. 49(4). 329-336 (2003)
• [文献書誌] Minako Kiso, Noboru Manabe, Kohji Komatsu, Munetake Shimabe, Hajime Miyamoto: "Abnormal structural luteolysis in ovaries of the senescence accelerated mouse (SAM) : expression of Fas Ligand/Fas-mediated apoptosis signaling molecules in luteal cells."Journal of Reproduction and Devevelopment. 49(6). 457-463 (2003)
• [文献書誌] Hanako Nishizawa, Noboru Manabe, Maki Morita, Miki Sugimoto, Satoshi Imanishi, Hajime Miyamoto: "Effects of in utero exposure of bisphenol A on expression of RARα and RXRα mRNAs in murine embryos."Journal of Reproduction and Devevelopment. 49(6). 539-545 (2003)
• [文献書誌] Kozue Uchio-Yamada, Noboru Manabe, Misuzu Yamaguchi-Yamada, Yasufumi Goto, Yoshie Yamamoto, Atsuo Ogura, Hajime Miyamoto: "Changes in the localization of type I, III and IV collagen mRNAs in the kidneys of hereditary nephritic (ICGN) mice with renal fibrosis."The Journal of Veterinary Medical Science. 66(2). 123-128 (2004)
• [文献書誌] Miki Sugimoto, Noboru Manabe, Maki Morita, Kei-Ichi Sezaki, Takako Tanaka, Satoshi Imanishi, Hanako Nishizawa, Mineko Iwahori, Hajime Miyamoto: "NMR spectroscopic assessment of effects of estrogenic compounds on male reproductive organs in mice."Biology of Reproduction. 67. 186 (2003)
• [文献書誌] Ysufumi Goto, Noboru Manabe, Kozue Uchio, Misuzu Yamaguchi-Yamada, Naoko Inoue, Yoshie Yamamoto, Atsuo Ogura, Nobuo Nagano, Hajime Miyamoto: "Myofibroblastic differentiation in tubulointerstitial cells is provoked by augmented cytoplasmic Smad4 protein in hereditary nephrotic ICGN mice with chronic renal fibrosis."Cell and Tissue Research. 315. 209-221 (2004)
• [文献書誌] Miki Sugimoto, Noboru Manabe, Hajime Miyamoto: "Cryopreservation of ovarian tissue."Igakuno Ayumi. 204(13). 921-925 (2003)
• [文献書誌] Noboru Manabe, Naoko Inoue, Chiemi Tajima, Toshikatsu Matsui, Shinsuke Nakagawa, Akihisa Maeda, Hajime Miyamoto: "Monoclonal antibodis recognize novel cell death receptors of granulosa cells in pig ovaries."Biology of Reproduction. 67. 234 (2003)
• [文献書誌] Naoko Inoue, Noboru Manabe, Toshikatsu Matsui, Shinsuke Nakagawa, Akihisa Maeda, Hajime Miyamoto: "Changes in expression of fas-dependent apoptotic signaling molecules in granulosa cells during folliclar atresia in pig ovaries."Biology of Reproduction. 67. 234 (2003)
• [文献書誌] Satoshi Imanishi, Noboru Manabe, Miki Sugimoto, Hajime Miyamoto: "Changes in mRNA expression of GPRC5B/RAIG2, a novel orphan receptor, in mouse placenta during late gestation."Biology of Reproduction. 67. 154 (2003)
• [文献書誌] Noboru Manabe, Naoko Inoue, Toshikatsu Matsui, Shinsuke Nakagawa, Akihisa Maeda, Takashi Miyano, Kazuhiro Sakamaki, Miki Sugimoto, Hajime Miyamoto: "Animal Frontier Science"Hokuto Pub.Co, Kyoto. 363 (2003)
• [文献書誌] Noboru Manabe, Satoko Wada, Naoko Inoue, Toshikatu Matsui, Shinsuke Nakagawa, Akihisa Maeda, Hajime Miyamoto: "Animal Frontier Science"Hokuto Pub.Co, Kyoto. 363 (2003)
• [文献書誌] Mizuho Nakayama, Noboru Manabe, Naoko Inoue, Toshikatsu Matsui, Shinsuke Nakagawa, Akihisa Maeda, Hajime Miyamoto: "Animal Frontier Science"Hokuto Pub.Co, Kyoto. 363 (2003)
• [文献書誌] Naoko Inoue, Noboru Manabe, Toshikatsu Matsui, Shinsuke Nakagawa, Hajime Miyamoto: "Animal Frontier Science"Hokuto Pub.Co, Kyoto. 363 (2003)
• [文献書誌] Miki Sugimoto, Noboru Manabe, Maki Morita, Satoshi Imanishi, Hanako Nishizawa, Mineko Iwahori, Hajime Miyamoto: "Animal Frontier Science"Hokuto Pub.Co, Kyoto. 363 (2003)
• [文献書誌] Noboru Manabe, Yasuyoshi Azuma, Miki Sugimoto, Satoshi Imanishi, Hanako Nishizawa, Maki Morita, Hajime Miyamoto: "Animal Frontier Science"Hokuto Pub.Co, Kyoto. 363 (2003)
• [文献書誌] Noboru Manabe, Naoko Inoue, Takashi Miyano, Kazuhiro Sakamaki, Miki Sugimoto, Hajime Miyamoto: "The Ovary, 2^<nd> edition"Academic Press/Elsevier Science, Amsterdam, The Nederland. 664 (2003)
• [文献書誌] Noboru Manabe: "Veterinary Histology 3^<rd> edition"Gakusoshya Pub.Co, Tokyo, Japan. 315 (2003)
• [文献書誌] Noboru Manabe: "Biology of Reproduction 2^<nd> edition"Asakura Pub.Co, Tokyo, Japan. 315 (2003)
• [文献書誌] Noboru Manabe, Minako Kiso, Munetake Shimabe, Hajime Miyamoto: "The Senescence-Accelerated Mouse (SAM) : An Animal Model of Senescence"Elsevier Science Publishers B.V., Amsterdam, The Nederland. 448 (2004)
• [文献書誌] Toshikatu Matsui, Noboru Manabe, Yasufumi Goto, Naoko Inoue, Shinsuke Nakagawa, Akihisa Maeda, Susumu Nishihara, Hajime Miyamoto: "Animal Frontier Science"Hokuto Pub.Co, Kyoto. 363 (2003)
• [文献書誌] Misuzu Yamaguchi-Yamada, Noboru Manabe, Kozue Uchio-Yamada, Naotsugu Akashi, Yasufumi Gotoh, Masaya Nagao, Yoshie Yamamoto, Atsuo Ogura, Hajime Miyamoto: "Animal Frontier Science"Hokuto Pub.Co, Kyoto. 363 (2003)
• [文献書誌] Minako Kiso, Noboru Manabe, Kohji Komatsu, Munetake Shimabe, Hajime Miyamoto: "Animal Frontier Science"Hokuto Pub.Co, Kyoto. 363 (2003)
• [文献書誌] Noboru Manabe, Kozue Yamada-Uchio, Misuzu Yamada-Yamaguchi, Yasufumi Gotoh, Toshiharu Mori, Chinatsu Sakata, Yoshihiro Furuya, Hajime Miyamoto: "Animal Frontier Science"Hokuto Pub.Co, Kyoto. 363 (2003)
• [文献書誌] Maki Morita, Miki Sugimoto, Takako Tanaka, Satoshi Imanishi, Hanako Nishizawa, Kei-Ichi Sezaki, Mineko Iwahori, Noboru Manabe, Hajime Miyamoto: "Animal Frontier Science"Hokuto Pub.Co, Kyoto. 363 (2003)
• [文献書誌] Munetake Shimabe, Minako Kiso, Kohji Komatsu, Noboru Manabe, Hajime Miyamoto: "The Senescence-Accelerated Mouse (SAM) : An Animal Model of Senescence"Elsevier Science Publishers B.V., Amsterdam, The Nederland. 448 (2004)
• [文献書誌] Minako Kiso, Munetake Shimabe, Kohji Komatsu, Noboru Manabe, Hajime Miyamoto: "The Senescence-Accelerated Mouse (SAM) : An Animal Model of Senescence"Elsevier Science Publishers B.V., Amsterdam, The Nederland. 448 (2004)
• [文献書誌] Morikawa Masahiro, Wakoto Matsuyama, Miki Sugimoto, Maki Morita, Aki Nakayama, Noboru Manabe, Shinsuke Morisawa: "Environmental Toxicity Evaluation and Risk Management"The Environment Risk Management Group of the JSPS-VCC Program on Environmental Science, Engineering and Ethics 2000-2009. Kyoto, Japan. 159 (2003)
• [文献書誌] Noboru Manabe, Minako Kiso, Munetake Shimabe, H.Miyamoto: "Proceedings of the 2^<nd> International Conference on Senescence : The SAM model"The Council for SAM Research, Sapporo, Japan. 120 (2003)
• [文献書誌] Munetake Shimabe, Minako Kiso, Noboru Manabe, Hajime Miyamoto: "Proceedings of the 2^<nd> International Conference on Senescence : The SAM model"The Council for SAM Research, Sapporo, Japan. 120 (2003)
• [文献書誌] Minako Kiso, Munetake Shimabe, Noboru Manabe, Hajime Miyamoto: "Proceedings of the 2^<nd> International Conference on Senescence : The SAM model"The Council for SAM Research, Sapporo, Japan. 120 (2003)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] Noboru Manabe: "Molecular mechanism of follicle selection in mammalian ovaries"Journal of Laboratory Animals (Kansai). 23・1. 71-78 (2002)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] Miki Sugimoto, Noboru Manabe, Hajime Miyamoto: "Cryopreservation techniques for ovarian tissues"Hormone Frontier in Gynecology. 9・1. 135-140 (2002)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] Satoko Wada, Noboru Manabe et al.: "TRAIL-decoy receptor-1 disappears in granulosa cells of atretic follicles in porcine ovaries"Journal of Reproduction and Devevelopment. 48・2. 167-173 (2002)
• [文献書誌] Satoko Wada, Noboru Manabe et al.: "TRADD is involved in apoptosis induction in granulosa cells during atresia in pig ovaries"Journal of Reproduction and Devevelopment. 48・2. 175-181 (2002)
• [文献書誌] Hitoshi Okamura, Noboru Manabe et al.: "Protein tyrosine kinase expression in the porcine ovary"Molecular Human Reproduction. 7・6. 723-729 (2001)
• [文献書誌] Eiichi Hondo, Noboru Manabe et al.: "Molecular cloning and expression of suppressor of potassium transport defect 3 (SKD3) in rat testis"Journal of Reproduction and Devevelopment. 47・2. 173-180 (2001)
• [文献書誌] Minako Kiso, Noboru Manabe et al.: "Abnormal accumulation of luteal bodies in ovaries of the senescence accelerated mouse (SAM)"Journal of Reproduction and Devevelopment. 47・2. 153-164 (2001)
• [文献書誌] Mizuho Nakayama, Noboru Manabe et al.: "Changes in localization of type I, III and IV collagens and their mRNA expression during follicular atresia in bovine and porcine ovaries"Journal of Reproduction and Devevelopment. 47・1. 27-31 (2001)
• [文献書誌] Noboru Manabe et al.: "A novel in vivo NMR technique to assess halocarbon induced hepatic failure in mice"Water Science and Technology. 17・1. 32-38 (2001)
• [文献書誌] Noboru Manabe et al.: "In vivo noninvasive nuclear magnetic resonance (NMR) technique for assessment of teratogenicity induced by chemicals"Chemical Engineering. 47・1. 110-114 (2002)
• [文献書誌] Miki Sugimoto, Noboru Manabe et al.: "Update on cryopreservation of mammalian ovaries"Obstetrics and Gynecology. 68・2. 207-212 (2001)
• [文献書誌] Noboru Manabe et al.: "A novel cell death receptor and a decoy receptor on follicular granulose cells of porcine ovaries"Japanese Journal of Embryo Transfer. 23・1. 52-60 (2001)
• [文献書誌] Naoko Inoue, Noboru Manabe et al.: "Elongation of cell cycle of early stage tetraploid murine embryos induced by cytochalasin B"Japanese Journal of Embryo Transfer. 23・1. 44-51 (2001)
• [文献書誌] Noboru Manabe et al.: "Physiological roles of apoptosis in granulosa cells of atretic follicles in porcine ovaries"Japanese Journal of Embryo Transfer. 23・1. 1-10 (2001)
• [文献書誌] Noboru Manabe et al.: "Monoclonal antibodies recognize a novel cell death receptor and a decoy receptor on granulosa cells of porcine ovarian follicles"Journal of Mammalian Ova Research. 18・1. 1-13 (2001)
• [文献書誌] Noboru Manabe et al.: "Immunohistochemical Quantification of fast-myosin in upper hind limp muscles of the pig"Animal Science Journal. 72・2. 154-163 (2001)
• [文献書誌] Hideki Tonomura, Nobor Manabe et al.: "Detection of rat model useful for genetic analysis of intramascular fat accumulation"Animal Genetic Journal. 2・1. 3-10 (2001)
• [文献書誌] Brussow K-P, Noboru Manabe et al.: "Biotechnological aspects of embryo transfer in swine"Hungarian Animal Breeding and Nutrition. 50・4. 481-493 (2001)
• [文献書誌] Noboru Manabe et al.: "Changes in quantitative profile of extracellular matrix components in the kidneys of rats with adriamycin-induced nephropathy"Journal of Veterinary Medical Science. 61・1. 125-133 (2001)
• [文献書誌] Misuzu Yamaguchi, Noboru Manabe et al.: "Localization of proliferative and apoptptic cells in the kidneys of ICR-derives glomerulonephritis (ICGN) mice"Journal of Veterinary Medical Science. 62・6. 781-787 (2001)
• [文献書誌] Kozue Uchio-Yamada, Noboru Manabe et al.: "Localization of extracellular matrix receptors in ICGN mice, a strain of mice with hereditary nephrotic syndrome"Journal of Veterinary Medical Science. 62・11. 1171-1178 (2002)
• [文献書誌] Malki Morita, Noboru Manabe et al.: "Changes in morphology of mouse oviduct ampulla during early pregnancy"Biology of Reproduction. 64・2. 325 (2001)
• [文献書誌] Noboru Manabe et al.: "Teratosis induced by retinoites to apoptotic cell death in mouse embryos"Miyamoto H, Manabe N (eds), Reproductive biotechnology update and its related physiology Hokuto Publishing Co., (Kyoto, Japan). 424 (2001)
• [文献書誌] Takako Tanaka, Noboru Manabet al.: "Effects of endocrine disruptersrts on the expression of nuclear receptors in murine embryos"Miyamoto H, Manabe N (eds), Reproductive Biotechnology : Reproductive biotechnology update and its related physiology(Hokuto Publishing Co., (Kyoto, Japan)). 424 (2001)
• [文献書誌] Miki Sugimoto, Noboru Manabe et al.: "Uilization of NMR microscopy in developmental toxicology : assessment of mouse embryo malformations induced by maternal administration of retinoic acid"Miyamoto H, Manabe N(eds), Reproductive Biotechnology : Reproductive biotechnology update and its related physiology(Hokuto Publishing Co., (Kyoto, Japan)). 424 (2001)
• [文献書誌] Noboru Manabe et al.: "Quantitative estimation of physiological properties by histochemical techniques"Miyamoto H, Manabe N(eds), Reproductive Biotechnology : Reproductive biotechnology update and its related physiology(Hokuto Publishing Co., (Kyoto, Japan)). 424 (2001)
• [文献書誌] Noboru Manabe et al.: "In vivo 31P-nuclear magnetic resonance technique for estibation of liver energy metabolism in mice"Miyamoto H, Manabe N(eds), Reproductive Biotechnology : Reproductive biotechnology update and its related physiology(Hokuto Publishing Co., (Kyoto, Japan)). 424 (2001)
• [文献書誌] Miki SUGIMOTO, Noboru Manabe et al.: "Histological and biochemical profiles of granulosa cell apoptosis in follicular atresia of porcine ovaries"Miyamoto H, Manabe N(eds), Reproductive Biotechnology : Reproductive biotechnology update and its related physiology(Hokuto Publishing Co., (Kyoto, Japan)). 424 (2001)
• [文献書誌] Noboru Manabe et al.: "Cell death receptor dependent regulation of granulosa cell apoptosis in porcine ovarian follicle atresia"Miyamoto H, Manabe N(eds), Reproductive Biotechnology : Reproductive biotechnology update and its related physiology(Hokuto Publishing Co., (Kyoto, Japan)). 424 (2001)
• [文献書誌] Mizuho Nakayama, Noboru Manabe et al.: "Histochemical studies for comparison of regulatory mechanisms of follicular development in mammmalian ovaries"Miyamoto H, Manabe N(eds), Reproductive Biotechnology : Reproductive biotechnology update and its related physiology(Hokuto Publishing Co., (Kyoto, Japan)). 424 (2001)
• [文献書誌] Namiko Kiso, Noboru Manabe et al.: "Abnormal accumulation of luteal bodies in ovaries of the senescence accelerated mouse(SAM)"Miyamoto H, Manabe N(eds), Reproductive Biotechnology : Reproductive biotechnology update and its related physiology(Hokuto Publishing Co., (Kyoto, Japan)). 424 (2001)
• [文献書誌] Maki Morita, Noboru Manabe et al.: "Functions of mammalian oviducts and their relevance to morphology"Miyamoto H, Manabe N(eds), Reproductive Biotechnology : Reproductive biotechnology update and its related physiology(Hokuto Publishing Co., (Kyoto, Japan)). 424 (2001)
• [文献書誌] Kozue Yamada-Uchio, Noboru Manabe et al.: "Abnormalities of extracellular matrix metabolisms in the kidney of ICGN mice, a strain of mice with hereditary nephrotic syndrome"Miyamoto H, Manabe N(eds), Reproductive Biotechnology : Reproductive biotechnology update and its related physiology(Hokuto Publishing Co., (Kyoto, Japan)). 424 (2001)
• [文献書誌] Misuzu Yamaguchi, Noboru Manabe et al.: "Renal anemia in ICR-derived glomerulonephritis (ICGN) mice"Miyamoto H, Manabe N(eds), Reproductive Biotechnology : Reproductive biotechnology update and its related physiology(Hokuto Publishing Co., (Kyoto, Japan)). 424 (2001)
• [文献書誌] Miki Sugimoto, Noboru Manabe et al.: "Cryopreservation of mammalian ovarian tissue"Miyamoto H, Manabe N(eds), Reproductive Biotechnology : Reproductive biotechnology update and its related physiology(Hokuto Publishing Co., (Kyoto, Japan)). 424 (2001)
• [文献書誌] 眞鍋昇: "雌性生殖器官"獣医組織学 第2版,日本獣医解剖学会編集(学窓社.東京.). 448 (2001)