YAMADA Mitsutoshi

写真a

Affiliation

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

Position

Associate Professor

External Links
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Career 【 Display / hide 】

  • 2013.01
    -
    2015.09

    The New York Stem Cell Foundation Research Institute, postdoctoral fellow

  • 2015.10
    -
    2016.03

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

  • 2016.04
    -
    2019.03

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

  • 2019.04
    -
    2024.06

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

  • 2024.07
    -
    Present

    慶應義塾大学, 准教授

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Academic Background 【 Display / hide 】

  • 1996.04
    -
    2002.03

    Keio University, School of Medicine

    University, Graduated

  • 2006.04
    -
    2010.03

    Keio University, School of Medicine

    Graduate School, Graduated

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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

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Licenses and Qualifications 【 Display / hide 】

  • 医師免許, 2002.04

  • 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

  • 日本産科婦人科学会認定産婦人科指導医, 2017.07

  • 日本生殖医学会生殖医療専門医, 2018.04

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Research Areas 【 Display / hide 】

  • Life Science / Developmental biology

  • Life Science / Genetics

  • Life Science / Medical biochemistry

  • Life Science / Obstetrics and gynecology

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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

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Books 【 Display / hide 】

  • 「基本から学ぶ不妊治療」 4. 不妊症の治療（１）不妊カップルに対する治療のアルゴリズム

    山田　満稔, 2024

    　View Summary

    研修ノート No.112, 日本産婦人科医会 2024

  • 『元気がいいね』 「医療のいまこれから：医療トピックス」 不妊治療

    山田　満稔 , 2023

    　View Summary

    東京都医師会広報誌

  • 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　加齢によって配偶子に起こる妊孕性変化　5. 反復着床不成功の原因と治療終結. 1) 加齢によって配偶子に起こる妊孕性変化. 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？生まれてくる子供への影響は？

    山田満稔, 医学書院, 2019.04

  • 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　5. 反復着床不成功の原因と治療終結. 1) 加齢によって配偶子に起こる妊孕性変化. Q88 女性の年齢が上がると、妊娠しにくくなるのでしょうか？生まれてくる子供への影響は？

    中川 亮, 山田 満稔, 2019.04

  • 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

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Papers 【 Display / hide 】

  • Calcium oscillations and mitochondrial enzymes in stem cells

    Fukuoka M., Kang W., Horiike S., Yamada M., Miyado K.

    Regenerative Therapy 26   811 - 818 2024.06

    　View Summary

    Calcium oscillations are rhythmic fluctuations of the intracellular concentration of calcium ions (Ca2+). As Ca2+ evokes various cellular processes, its intracellular concentration is tightly regulated. Ca2+ oscillations control biological events, including neuronal differentiation and proliferation of mesenchymal stem cells. The frequency and pattern of Ca2+ oscillations depend on cell type. Researchers have studied Ca2+ oscillations to better understand how cells communicate and regulate physiological processes. Dysregulation of Ca2+ oscillations causes health problems, such as neurodegenerative disorders. This review discusses the potential functions of Ca2+ oscillations in stem cells.

  • Overdue Calcium Oscillation Causes Polyspermy but Possibly Permits Normal Development in Mouse Eggs

    Fukuoka M., Kang W., Katano D., Horiike S., Miyado M., Tanaka M., Miyado K., Yamada M.

    International Journal of Molecular Sciences (International Journal of Molecular Sciences)  25 ( 1 )  2024.01

    ISSN  16616596

    　View Summary

    In some non-mammalian eggs, the fusion of one egg and multiple sperm (polyspermy) induces a robust rise in intracellular calcium ion (Ca2+) concentration due to a shortage of inducers carried by a single sperm. Instead, one of the sperm nuclei is selected inside the egg for normal embryogenesis. Polyspermy also occurs during the in vitro fertilization of human eggs; however, the fate of such eggs is still under debate. Hence, the relationship between polyspermy and repetitive Ca2+ increases (Ca2+ oscillation) in mammals remains unknown. To address this issue, we used mouse sperm lacking extramitochondrial citrate synthase (eCS), which functions as a Ca2+ oscillation inducer; its lack causes retarded Ca2+ oscillation initiation (eCs-KO sperm). Elevated sperm concentrations normalize Ca2+ oscillation initiation. As expected, eCS deficiency enhanced polyspermy in both zona pellucida (ZP)-free and ZP-intact eggs despite producing the next generation of eCs-KO males. In conclusion, similarly to non-mammalian eggs, mouse eggs may develop normally under polyspermy conditions caused by problematic Ca2+ oscillation.

  • Assessment of embryologist sufficiency and associated regional disparities in Japanese assisted reproduction facilities using nationwide survey data (IZANAMI project)

    Shirasawa H., Yamada M., Jwa S.C., Kuroda K., Harada M., Osuga Y.

    Journal of Obstetrics and Gynaecology Research (Journal of Obstetrics and Gynaecology Research)   2024

    ISSN  13418076

    　View Summary

    Aims: This study aims to comprehensively examine the employment and practices of embryologists in Japan's assisted reproductive technology (ART) laboratories, focusing on the impact of various factors such as ART cycle numbers, add-ons, and regional differences. Additionally, it seeks to assess the extent to which Japanese ART facilities meet international minimum standards set by the American Society for Reproductive Medicine (ASRM). Methods: A survey was conducted from December 2021 to February 2022 among 621 ART facilities in Japan. The study categorized facilities into five ART cycle groups and compared the number of embryologists across these groups. It also examined the correlation between the number of embryologists, ART cycles, add-ons, and regional differences. Data were analyzed using linear regression and multiple linear regression analyses. Results: The study's findings revealed a significant correlation between the total number of embryologists at each facility and the ART cycles. Notably, there were significant differences in the number of embryologists across all ART cycle categories. Of the 435 facilities, only 44.6% met the ASRM minimum embryologist staffing requirement. The regression analysis further highlighted the significance of ART cycles and preimplantation genetic testing for aneuploidies as factors. Moreover, the number of embryologists stationed at urban facilities was significantly higher than at nonurban facilities, indicating a potential regional disparity. Conclusion: In Japan, it was first found that more than 50% of ART facilities do not have sufficient embryologists in place relative to the number of ART cycles. Furthermore, the add-ons and regional differences affect the placement of embryologists.

  • Variation in diagnostic methods, criteria, and treatment for chronic endometritis: A nationwide survey in Japan

    Jwa S.C., Kuroda K., Shirasawa H., Harada M., Osuga Y., Yamada M.

    Journal of Obstetrics and Gynaecology Research  2024

    ISSN  13418076

    　View Summary

    Aim: To investigate variation in the diagnosis and treatment of chronic endometritis (CE) at the national level in Japan. Methods: We performed a nationwide survey targeting all assisted reproductive technology (ART) facilities across Japan between 2021 and 2022. Diagnostic methods, criteria, and first- and second-line treatment protocols for CE were collected via a questionnaire. Results: Among 616 ART facilities, 437 responded to the survey (response rate: 70.9%) of which 339 (77.6%) implemented diagnosis and treatment of CE. In the diagnosis of CE, 214 (63.1%) facilities used CD138 immunohistochemical staining of endometrial tissue, while hysteroscopy was the most frequently used as an adjunct diagnostic method (241 facilities, 71.1%). The most frequent cutoff value of CD138-positive cells for diagnosing CE was 3–5 cells/20 high-power fields (50%), but 7.9% (17 facilities) and 5.1% (11 facilities) used cutoff values of 1 and 2 cells, respectively. The most common first- and second-line treatment methods were doxycycline (210 facilities, 61.9%) and ciprofloxacin + metronidazole (164 facilities, 48.0%), respectively. Conclusions: There is considerable variation in the number of CD138-positive cells used for diagnosing CE. Establishing unified diagnostic criteria and therapeutic methods for CE is essential to provide standardized medicine for CE at the national level.

  • Fertility preservation after gonadotoxic treatments for cancer and autoimmune diseases

    Saito S., Yamada M., Yano R., Takahashi K., Ebara A., Sakanaka H., Matsumoto M., Ishimaru T., Utsuno H., Matsuzawa Y., Ooka R., Fukuoka M., Akashi K., Kamijo S., Hamatani T., Tanaka M.

    Journal of Ovarian Research (Journal of Ovarian Research)  16 ( 1 )  2023.12

    　View Summary

    Background: The indications for fertility preservation (FP) have expanded. A few patients who underwent gonadotoxic treatment did not have the opportunity to receive FP, leading to concerns that these patients may develop premature ovarian insufficiency. However, the usefulness of FP in women with reduced ovarian reserve has also been questioned. Progestin-primed ovarian stimulation can improve the controlled ovarian stimulation (COS) protocol, but there is limited data on the efficacy of FP with progestin-primed ovarian stimulation. Methods: We conducted a prospective study of 43 women with cancer or autoimmune diseases before and after gonadotoxic treatment at the reproductive unit of Keio University Hospital, counselled between 1 January 2018 and 31 December 2021. After counselling, informed consent was obtained for FP from 43 patients, with those who underwent gonadotoxic treatment of the primary disease being prioritised. Gonadotropin-releasing hormone analogue or progestin was used to suppress luteinising hormone in COS before or after gonadotoxic treatment. The number of cryopreserved mature oocytes was the primary outcome. Results: Forty-three patients and 67 assisted reproductive technology cycles were included in the analysis. The median age at entry was 32 [inter quartile range (IQR), 29–37] years. All patients in the post-gonadotoxic treatment group had their oocytes frozen. Gonadotoxic treatment resulted in fewer oocytes [median 3 (IQR 1–4); pre-gonadotoxic treatment group: five patients, 13 cycles] vs. median 9 (IQR 5–14; pre-gonadotoxic treatment group: 38 patients, 54 cycles; P < 0.001). Although anti-Müllerian hormone levels were lower in the post-gonadotoxic treatment group (n = 5, 13 cycles, median 0.29 (IQR 0.15–1.04) pg/mL) than in the pre-gonadotoxic treatment group (n = 38, 54 cycles, median 1.89 (IQR 1.15–4.08) pg/mL) (P = 0.004), oocyte maturation rates were higher in the post-gonadotoxic treatment group [median 100 (IQR 77.5–100) %] than in the pre-gonadotoxic group [median 90.3 (IQR 75.0–100) %; P = 0.039]. Five patients in the pre-gonadotoxic treatment group had their cryopreserved embryos thawed, of which three had live births. Conclusions: Oocytes obtained for FP from women with cancer or autoimmune disease for FP are of satisfactory quality, regardless of whether they are obtained post-gonadotoxic treatment or COS protocols.

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

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Reviews, Commentaries, etc. 【 Display / hide 】

  • Guidelines for Reproductive Medicine in Japan

    Yamada M., Ishikawa T., Iwasa T., Oishi H., Osuka S., Oka K., Ono S., Ono M., Orisaka M., Kanasaki H., Kawano Y., Kawamura K., Kishi H., Kimura F., Kuroda S., Kuwahara A., Kobayashi H., Komiya A., Saito H., Sato K., Sato S., Shiraishi K., Shirasawa H., Suzuki T., Takai Y., Takae S., Takahashi T., Takiuchi T., Tachibana M., Tamura I., Tamura H., Jwa S.C., Baba T., Harada M., Hirata T., Fukui A., Fukuda Y., Fukuhara S., Maruyama T., Yumura Y., Yoshino O., Hirota Y., Tsujimura A., Kuji N., Osuga Y.

    Reproductive Medicine and Biology (Reproductive Medicine and Biology)  21 ( 1 )  2022.01

    ISSN  14455781

  • Mitochondrial replacement by genome transfer in human oocytes - efficacy, concerns and legality

    Yamada M*, Sato S, Ooka R, Akashi K, Nakamura A, Miyado K, Akutsu H, Tanaka M

    Reproductive Medicine and Biology 20 ( 1 ) 53 - 61 2021

    Article, review, commentary, editorial, etc. (scientific journal), Lead author, Corresponding author

  • Mitochondria genetic drift after nuclear transfer in oocytes

    Yamada M, Akashi K, Ooka R, Miyado K, Akutsu H

    International Journal of Molecular Sciences 21 ( 16 ) 5880 2020

    Article, review, commentary, editorial, etc. (scientific journal), Lead author, Corresponding author

  • 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

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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

    2023.06
    -
    2029.03

    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

    2020.04
    -
    2025.03

    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

    2017.04
    -
    2020.03

    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

    2009.04
    -
    2012.03

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

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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

    2018.01

  • 平成29年度日本生殖医学会学術奨励賞

    2017.11

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

    2017.06

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

    2017.06

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Courses Taught 【 Display / hide 】

  • LECTURE SERIES, OBSTETRICS

    2024

  • LECTURE SERIES, OBSTETRICS

    2023

  • LECTURE SERIES, OBSTETRICS

    2022

  • LECTURE SERIES, OBSTETRICS

    2021

  • LECTURE SERIES, OBSTETRICS

    2020

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Courses Previously Taught 【 Display / hide 】

  • 性周期のモニタリング

    Keio University

    2018.04
    -
    2019.03

  • 生殖細胞の発生、受精・着床・妊娠の成立

    Keio University

    2018.04
    -
    2019.03

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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
    -
    Present

    代議員, 社団法人　日本生殖医学会

  • 2017.04
    -
    2019.03

    代議員, 日本卵子学会

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