Hamatani, Toshio



School of Medicine, Department of Obstetrics and Gynecology (Obstetrics) (Shinanomachi)


Assistant Professor/Senior Assistant Professor

External Links

Career 【 Display / hide

  • 2005.07

    2005(Jul.)- Instructor in Dept. Obstetrics and Gynecology. Keio University School of Medicine. 2004(Aug.)-2005(Jun.) Instructor in Dept. Obstetrics and Gynecology. Tokyo Women’s Medical Uni

Academic Background 【 Display / hide

  • 1992.03

    Keio University, Faculty of Medicine

    University, Graduated

Academic Degrees 【 Display / hide

  • M.D., Ph.D., Keio University, Dissertation, 2000.10


Research Areas 【 Display / hide

  • Developmental biology (Developmental Biology)

  • Genetics/Chromosome dynamics (Heredity/Genome Dynamics)

  • Obstetrics and gynecology (Obstetrics and Gynecology)


Books 【 Display / hide

  • 臨床検査ガイド2013年版(編集:Medical Practice編集委員会)

    HAMATANI TOSHIO, 文光堂, 2013

    Scope: 461-465

  • 治療薬Up-To-Date 2013年版 ポケット判(監修:矢崎義雄,編集:松澤佑次,奥村勝彦,永井良三,千葉勉,伊藤貞嘉)

    HAMATANI TOSHIO, メディカルレビュー社, 2013

    Scope: 508-517

  • 生殖卵巣学-基礎知識と臨床の進展(編集:石塚文平、鈴木秋悦)

    HAMATANI TOSHIO, 医歯薬出版, 2011

    Scope: 236-243

  • 臨床検査ガイド2011年度版

    HAMATANI TOSHIO, 光文堂, 2011

  • 治療薬Up-To-Date 2009 ポケット判

    浜谷 敏生、吉村泰典, 2009

    Scope: 429- 438

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Papers 【 Display / hide

  • Zscan5b Deficiency Impairs DNA Damage Response and Causes Chromosomal Aberrations during Mitosis

    Ogawa S., Yamada M., Nakamura A., Sugawara T., Nakamura A., Miyajima S., Harada Y., Ooka R., Okawa R., Miyauchi J., Tsumura H., Yoshimura Y., Miyado K., Akutsu H., Tanaka M., Umezawa A., Hamatani T.

    Stem Cell Reports (Stem Cell Reports)  12 ( 6 ) 1366 - 1379 2019.06

    ISSN  22136711

     View Summary

    © 2019 The Authors Zygotic genome activation (ZGA) begins after fertilization and is essential for establishing pluripotency and genome stability. However, it is unclear how ZGA genes prevent mitotic errors. Here we show that knockout of the ZGA gene Zscan5b, which encodes a SCAN domain with C2H2 zinc fingers, causes a high incidence of chromosomal abnormalities in embryonic stem cells (ESCs), and leads to the development of early-stage cancers. After irradiation, Zscan5b-deficient ESCs displayed significantly increased levels of γ-H2AX despite increased expression of the DNA repair genes Rad51l3 and Bard. Re-expression of Zscan5b reduced γ-H2AX content, implying a role for Zscan5b in DNA damage repair processes. A co-immunoprecipitation analysis showed that Zscan5b bound to the linker histone H1, suggesting that Zscan5b may protect chromosomal architecture. Our report demonstrates that the ZGA gene Zscan5b is involved in genomic integrity and acts to promote DNA damage repair and regulate chromatin dynamics during mitosis. In this article, Yamada and colleagues show that Zscan5b deficiency increases DNA stress, compromises chromosomal structure during mitosis, and leads to the development of early-stage cancers. Zscan5b deficiency may offer a murine model of human chromosomal breakage syndromes.

  • Membrane protein CD9 is repositioned and released to enhance uterine function

    Iwai M., Hamatani T., Nakamura A., Kawano N., Kanai S., Kang W., Yoshii N., Odawara Y., Yamada M., Miyamoto Y., Saito T., Saito H., Miyado M., Umezawa A., Miyado K., Tanaka M.

    Laboratory Investigation (Laboratory Investigation)  99 ( 2 ) 200 - 209 2019.02

    ISSN  00236837

     View Summary

    © 2018, United States & Canadian Academy of Pathology. Tetraspanin CD9 is essential for sperm–egg fusion and also contributes to uterine repair through microexosome formation. Microexosomes share CD9 with exosomes and are released from eggs and uterine epithelial cells. However, the mechanism for the formation of microexosomes remains unknown. To address this issue, we examined membrane localization and extracellular release of CD9 proteins using uterine epithelial cells and secretions in mice and humans. In mice, CD9 localized predominantly on the basal region of the plasma membrane and relocated to the apical region upon embryo implantation. Furthermore, extracellular CD9 proteins were detected in uterine secretions of mice and women undergoing infertility treatment, but were below detectable levels in supernatants of pluripotent stem cells. Ultrastructural analysis demonstrated that membrane projections were shortened and the number of mitochondria was reduced in uterine epithelial cells lacking Cd9 genes. Our results suggest that CD9 repositioning and release affect both membrane structures and mitochondrial state in the uterus, and contribute to female fertility.

  • Chemotactic behavior of egg mitochondria in response to sperm fusion in mice

    Iwai M., Harada Y., Miyabayashi R., Kang W., Nakamura A., Kawano N., Miyamoto Y., Yamada M., Hamatani T., Miyado M., Yoshida K., Saito H., Tanaka M., Umezawa A., Miyado K.

    Heliyon (Heliyon)  4 ( 11 )  2018.11

    ISSN  24058440

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    © 2018 The Authors Mitochondria are the powerhouses of eukaryotic cells and their positioning contributes to fertilization and early developmental processes. We report that sperm fusion triggers Ca2+ oscillations and mitochondrial movement toward fused sperm (mitochondrial chemotaxis) in mouse eggs. Mitochondria functioned in Ca2+ storage and were colocalized with endoplasmic reticulum (ER) during Ca2+ oscillations. Mitochondria then moved toward the fused sperm. Sperm extracts lacking nuclei induced Ca2+ oscillations, but did not promote mitochondrial chemotaxis. Our results suggest that sperm fusion motivates Ca2+ oscillation-independent mitochondrial chemotaxis. This phenomenon indicates that egg mitochondria interact with sperm materials, presumably nuclear substances, and their network tethers egg and sperm nuclei at the early stage of zygote formation.

  • Degradation of phosphate polymer polyP enhances lactic fermentation in mice

    Nakamura, Akihiro, Kawano, Natsuko, Motomura, Kei, Kuroda, Akio, Sekiguchi, Kiyoshi, Miyado, Mami, Kang, Woojin, Miyamoto, Yoshitaka, Hanai, Maito, Iwai, Maki, Yamada, Mitsutoshi, Hamatani, Toshio, Saito, Takakazu, Saito, Hidekazu, Tanaka, Mamoru, Umezawa, Akihiro, Miyado, Kenji

    GENES TO CELLS (Genes to Cells)  23 ( 10 ) 904 - 914 2018.10

    Research paper (scientific journal),  ISSN  1356-9597

     View Summary

    © 2018 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd In bacteria, a polymer of inorganic phosphate (Pi) (inorganic polyphosphate; polyP) is enzymatically produced and consumed as an alternative phosphate donor for adenosine triphosphate (ATP) production to protect against nutrient starvation. In vertebrates, polyP has been dismissed as a “molecular fossil” due to the lack of any known physiological function. Here, we have explored its possible role by producing transgenic (TG) mice widely expressing Saccharomyces cerevisiae exopolyphosphatase 1 (ScPPX1), which catalyzes hydrolytic polyP degradation. TG mice were produced and displayed reduced mitochondrial respiration in muscles. In female TG mice, the blood concentration of lactic acid was enhanced, whereas ATP storage in liver and brain tissues was reduced significantly. Thus, we suggested that the elongation of polyP reduces the intracellular Pi concentration, suppresses anaerobic lactic acid production, and sustains mitochondrial respiration. Our results provide an insight into the physiological role of polyP in mammals, particularly in females.

  • Autophagy-disrupted LC3 abundance leads to death of supporting cells of human oocytes

    Kang W., Ishida E., Yamatoya K., Nakamura A., Miyado M., Miyamoto Y., Iwai M., Tatsumi K., Saito T., Saito K., Kawano N., Hamatani T., Umezawa A., Miyado K., Saito H.

    Biochemistry and Biophysics Reports (Biochemistry and Biophysics Reports)  15   107 - 114 2018.09

     View Summary

    © 2018 The Authors Autophagic recycling of cell parts is generally termed as the opposite of cell death. Here, we explored the relation between cell death and autophagy by examining granulosa cell layers that control oocyte quality, which is important for the success of fertilization. Granulosa cell layers were collected from infertile women and morphologically divided into four types, viz., mature (MCCs), immature (ICCs), and dysmature cumulus cells (DCCs), and mural granulosa cells (MGCs). Microtubule-associated protein light chain 3 (LC3), which is involved in autophagosome formation, was expressed excessively in DCCs and MGCs, and their chromosomal DNA was highly fragmented. However, autophagy initiation was limited to MGCs, as indicated by the expression of membrane-bound LC3-II and autophagy-related protein 7 (ATG7), an enzyme that converts LC3-I to LC3-II. Although pro-LC3 was accumulated, autophagy was disabled in DCCs, resulting in cell death. Our results suggest the possibility that autophagy-independent accumulation of pro-LC3 proteins leads to the death of human granulosa cells surrounding the oocytes and presumably reduces oocyte quality and female fertility.

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Papers, etc., Registered in KOARA 【 Display / hide

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Reviews, Commentaries, etc. 【 Display / hide

  • 精子・卵子保存法の現在-「産む」選択肢をあきらめないために】配偶子保存の必要性と課題 化学療法・放射線療法の妊孕性への影響.


    臨床婦人科産科 72 ( 5 ) 410 - 416 2018.05

    Introduction and explanation (commerce magazine), Joint Work

  • 【産婦人科外来パーフェクトガイド-いまのトレンドを逃さずチェック!】 疾患編 不妊・不育《人工授精》 提供精子を用いた人工授精(AID).


    臨床婦人科産科 72 ( 4 ) 163 - 166 2018.04

    Introduction and explanation (commerce magazine), Joint Work

  • 産婦人科領域と炎症(青木大輔編著) 不妊治療における慢性炎症と着床不全


    別冊Bio Clinica: 慢性炎症と疾患 (北隆館)  6 ( 4 ) 78 - 83 2017.11

    Introduction and explanation (commerce magazine), Joint Work

  • 【産婦人科診療で用いられるバイオマーカー】 抗ミュラー管ホルモン(anti-Muellerian hormone;AMH)と不妊


    産婦人科の実際 66 ( 10 ) 1189 - 1196 2017.10

    Introduction and explanation (commerce magazine), Joint Work

  • 【産婦人科におけるリスクマネジメント】 生殖医療におけるリスク


    産婦人科の実際 66 ( 6 ) 781 - 786 2017.06

    Introduction and explanation (commerce magazine)

Presentations 【 Display / hide

  • 基調講演「ドナー精子を用いた人工授精(AID/DI)の現況と課題」


    第152回関東生殖医学会 (四谷、東京) , 2018.07, Oral Presentation(key), 関東生殖医学会

  • Zfp371 is a novel DNA repair gene responsible for genome stability during mitosis.

    Seiji Ogawa, Mitsutoshi Yamada, TOSHIO HAMATANI, Hidenori Akutsu, Akihiro Umezawa, Mamoru Tanaka, Daisuke Aoki.

    The 70th Annual Congress of the Japan Society of Obstetrics and Gynecology (May 10-13, 2018) (SENDAI INTERNATIONAL CENTER, MIYAGI, JAPAN) , 2018.05, Oral Presentation(general)

  • 当院における妊孕性温存を目的とした精子凍結保存の現状と課題.


    第62回日本生殖医学会学術講演会(2017年11月16-17日) (下関市生涯学習プラザ・海峡メッセ下関) , 2017.11

  • 当院における若年男性悪性骨軟部腫瘍患者に対する精子凍結保存の現状と課題


    第55回日本癌治療学会学術集会(会期10月20-22日) (パシフィコ横浜) , 2017.10

  • シンポジウム「卵子の成熟と老化 -最新知見-」: 卵子加齢機構の探索と臨床への示唆


    第35回日本受精着床学会総会・学術講演会 (米子(鳥取県)) , 2017.07, Symposium, Workshop, Panelist (nomination), 日本受精着床学会(会期:2017年7月20-21日)

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 胚および子宮内膜由来の細胞外分泌顆粒に着目した着床不全の病態解明と新規治療法開発


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 浜谷 敏生, Grant-in-Aid for Scientific Research (B), Principal Investigator

  • 生殖とエクソソーム:卵成熟、受精、胚発生、着床におけるクロストーク機構の解明


    Grant-in-Aid for Scientific Research, 浜谷敏生, Research grant, Principal Investigator

  • 卵子の老化および生殖細胞、卵巣の凍結保存に関する研究 分担課題:成熟卵胞内エクソソームの加齢変化


    Japan Agency for Medical Research and Development (AMED), Health and Labour Sciences Research Grants, 東京大学・大学院医学系研究科・産婦人科学・教授・大須賀 穣, Research grant, Co-investigator

  • 卵子加齢の分子特性解明と新しいバイオマーカー開発の橋渡し研究


    Grant-in-Aid for Scientific Research, 国立成育医療研究センター・生殖・細胞医療研究部・阿久津英憲, Research grant, Co-investigator

  • 着床前期胚における「ゲノムの若返り」機構の解明


    Grant-in-Aid for Scientific Research, 浜谷敏生, Research grant, Principal Investigator

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Awards 【 Display / hide

  • 第47回日本哺乳動物卵子学会 学術奨励賞 基礎部門

    HAMATANI TOSHIO, 2006.05, 日本哺乳動物卵子学会, マウス着床遅延モデルを用いた胚性着床因子の網羅的検討

    Type of Award: Awards of National Conference, Council and Symposium

  • 三四会奨励賞

    HAMATANI TOSHIO, 2005.11, 慶應義塾大学医学部三四会, 着床前期胚の遺伝子発現プロファイリングとその動態解析

    Type of Award: Keio commendation etc.

  • Excellent Oral Presentation Award (The 57th Annual Congress of Japan Society of Obstetrics and Gynecology, Apr. 4, 2005)

    HAMATANI TOSHIO, 2005.04, Dynamics of global gene expression changes during mouse preimplantation development

    Type of Award: Awards of National Conference, Council and Symposium

  • Shock Award (NIA Post-Doctoral Retreat Talk Winner, Sep. 17, 2003)

    HAMATANI TOSHIO, 2003.09, Aging in Oocytes

    Type of Award: Other Awards

  • Serono Foundation Laureates - Reproductive Endocrinology Fellowship 2002(Feb.)-2004(Jan.)

    HAMATANI TOSHIO, 2001.07, Developmental Mechanism of Preimplantation Embryo in Mouse Using NIA 15K cDNA microarray

    Type of Award: Awards of Publisher, Newspaper Company and Foundation


Courses Taught 【 Display / hide











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Memberships in Academic Societies 【 Display / hide

  • Human Reproduction Update, 

  • 日本産科婦人科学会

  • 日本不妊学会

  • 日本内分泌学会

  • 日本哺乳動物卵子学会


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Committee Experiences 【 Display / hide

  • 2009.01

    Associate editor, Human Reproduction Update