YAMADA Mitsutoshi



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


Assistant Professor/Senior Assistant Professor

External Links

Career 【 Display / hide

  • 2013.01

    The New York Stem Cell Foundation Research Institute, postdoctoral fellow

  • 2015.10

    Tokyo Dental College, Ichikawa General Hospital, Department of Obstetrics and Gynecology, Assistant Professor

  • 2016.04

    Keio University, School of Medicine, Department of Obstetrics and Gynecology, Assistant Professor

  • 2019.04

    Keio University, School of Medicine, Department of Obstetrics and Gynecology, Assistant professor

Academic Background 【 Display / hide

  • 1996.04

    Keio University, School of Medicine

    University, Graduated

  • 2006.04

    Keio University, School of Medicine

    Graduate School, Graduated

Academic Degrees 【 Display / hide

  • 博士(医学), Keio University, National Institution for Academic Degrees and University Evaluation, 2010.03

    Involvement of a novel preimplantation-specific gene encoding the high mobility group box protein Hmgpi in early embryonic development

Licenses and Qualifications 【 Display / hide

  • 医師免許, 2006.04

  • 日本産科婦人科学会専門医, 2007.04

  • 日本人類遺伝学会専門医, 2012.04

  • 日本生殖医学会生殖医療専門医, 2018.04

  • 日本女性医学会ヘルスケア専門医, 2019.04


Research Areas 【 Display / hide

  • Life Science / Developmental biology

  • Life Science / Genetics

  • Life Science / Medical biochemistry

  • Life Science / Obstetrics and gynecology

Research Keywords 【 Display / hide

  • ミトコンドリア

  • リプログラム

  • 初期胚発生

  • 生殖医学


Books 【 Display / hide

  • 今すぐ知りたい! 不妊治療Q&A-基礎理論からDecision Makingに必要なエビデンスまで

    山田満稔, 中川亮, 医学書院, 2019.04

    Scope: 加齢によって配偶子に起こる妊孕性変化

  • 今すぐ知りたい! 不妊治療Q&A-基礎理論からDecision Makingに必要なエビデンスまで


    Scope: Q87 男性の年齢が上がると, 妊娠しにくくなるのでしょうか? 生まれてくる子どもへの影響は?

  • 新 不妊ケアABC 卵巣刺激法について簡単に説明してください

    山田満稔, 中川亮, 医歯薬出版株式会社, 2019.03

  • 先端医療シリーズ48「臨床医のための最新産科婦人科」4.体細胞核移植胚性幹細胞の樹立の意義

    YAMADA Mitsutoshi, 寺田国際事務所/ 先端医療技術研究所, 41-43, 2017, 2017

  • 【構造と機能】生殖腺の発生と性分化. よくわかる病態生理(監修:松尾理)第12巻婦人科疾患(編集:久保田俊郎)

    YAMADA Mitsutoshi, 日本医事新報社, 2009

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Papers 【 Display / hide

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

    Ogawa S., Yamada M*(corresponding author)., 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

     View Summary

    © 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 Ca 2+ oscillations and mitochondrial movement toward fused sperm (mitochondrial chemotaxis) in mouse eggs. Mitochondria functioned in Ca 2+ storage and were colocalized with endoplasmic reticulum (ER) during Ca 2+ oscillations. Mitochondria then moved toward the fused sperm. Sperm extracts lacking nuclei induced Ca 2+ oscillations, but did not promote mitochondrial chemotaxis. Our results suggest that sperm fusion motivates Ca 2+ 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 A, Kawano N, Motomura K, Kuroda A, Sekiguchi K, Miyado M, Woojin K, Miyamoto Y, Hanai M, Iwai M, Yamada M, Hamatani T, Saito T, Saito H, Tanaka M, Umezawa A, Miyado K.

    Genes Cells (Genes to Cells)  23 ( 10 ) 904 - 914 2018

    Joint Work,  ISSN  13569597

     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.

  • Genome Transfer Prevents Fragmentation and Restores Developmental Potential of Developmentally Compromised Postovulatory Aged Mouse Oocytes.

    YAMADA MitsutoshiDieter Egli

    Stem Cell Rep 8 ( 3 ) 576 - 588 2017

    Research paper (scientific journal), Joint Work

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

Reviews, Commentaries, etc. 【 Display / hide

  • Towards further optimization of preimplantation embryo culture media: from the viewpoint of omics and somatic cell nuclear transfer (SCNT) studies.

    Yamada M* (corresponding author), Hamatani T, Akutsu H, Tanaka M

    Journal of Mammalian Ova Research 33 ( 1 ) 35 - 43 2016.04

    Article, review, commentary, editorial, etc. (scientific journal), Joint Work

  • From cloned frogs to patient matched stem cells: induced pluripotency or somatic cell nuclear transfer?

    Yamada M, Byrne J, Egli D

    Current Opinion in Genetics & Development 34   29 - 34 2015.04

    Article, review, commentary, editorial, etc. (scientific journal), Joint Work

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

  • 生殖器官の共生細菌叢と細菌性代謝産物を介したヒト生命萌芽の分子機構の解明


    挑戦的研究(開拓), Principal investigator

  • 全能性獲得へのロードマップ:幹細胞のミトコンドリア・ゲノム安定性機構の解明


    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Principal investigator

  • ヒト初期胚発生型リプログラミングによるがん化しない安定したiPS細胞の樹立


    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Young Scientists (A), Principal investigator

  • Elucidation of the molecular mechanism of the human embryo development


    若手研究(B), Research grant, Principal investigator

Awards 【 Display / hide

  • 平成30年度日本医師会医学研究奨励賞

    2018.11, 日本医師会

  • 第22回 坂口光洋記念慶應義塾医学振興基金 医学研究奨励賞


  • 平成29年度日本生殖医学会学術奨励賞


  • International Society Stem Cell Research (ISSCR) 2017 Annual Meeting Merit Award


  • International Society Stem Cell Research (ISSCR) 2017 Annual Meeting Travel Award


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Courses Taught 【 Display / hide











Courses Previously Taught 【 Display / hide

  • 生殖細胞の発生、受精・着床・妊娠の成立

    Keio University


  • 性周期のモニタリング

    Keio University



Memberships in Academic Societies 【 Display / hide

  • International Society for Stem Cell Research

  • 日本産科婦人科学会

  • 日本生殖医学会

  • 日本卵子学会

  • 日本人類遺伝学会


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Committee Experiences 【 Display / hide

  • 2018.04

    代議員, 社団法人 日本生殖医学会

  • 2017.04

    代議員, 日本卵子学会