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

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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 】

  • 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

    2019.04

    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 】

  • 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.

  • 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.

  • Fact-finding survey on assisted reproductive technology in Japan

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

    Journal of Obstetrics and Gynaecology Research （Journal of Obstetrics and Gynaecology Research)  49 （ 11 ） 2593 - 2601 2023.11

    ISSN  13418076

    　View Summary

    Aims: In anticipation of the future development of assisted reproductive technology (ART) and to smoothly introduce new technology, it is necessary to understand the current staffing status of the medical system and the current state of treatment, as well as the status of in vitro fertilization add-ons, where the need for insurance coverage is currently a matter of debate. Methods: ART facilities in Japan were surveyed (437 valid responses, response rate: 71%). Current staffing status of the medical system, implementation rates of ART, add-on treatments, and medical supplies were investigated. Results: Despite the abundance of embryologists, nurses, and obstetricians and gynecologists in facilities, the majority of facilities lacked counselors, anesthesiologists, and other essential medical professionals. Conventional ovarian stimulation was widely adopted (median 120 [interquartile range 60–300] cycles), followed by mild ovarian simulation (60 [30–200]). Additionally, freeze–thaw embryo transfer cycles (300 [120–750]) were performed more frequently than fresh embryo transfer cycles (30 [30–60]). Among the add-ons, assisted hatching (85.1%), chronic endometritis examination (77.2%) and treatment (76.9%), artificial oocyte activation (67.3%), endometrial receptivity analysis (64.2%), and endometrial microbiome analysis (58.9%) were relatively widely employed. Conclusions: The implementation of frozen–thawed embryo transfer cycles, freeze-all strategies, and add-on treatments have become popular and widely accepted despite the lack of robust evidence regarding their safety and efficacy.

  • Sodium Hexametaphosphate Serves as an Inducer of Calcium Signaling

    Katano D., Kang W., Harada Y., Kawano N., Miyado M., Saito T., Fukuoka M., Yamada M., Miyado K.

    Biomolecules （Biomolecules)  13 （ 4 ）  2023.04

    　View Summary

    In bacteria, polymers of inorganic phosphates, particularly linear polyphosphate, are used as alternative phosphate donors for adenosine triphosphate production. A six-chain form of sodium metaphosphate, sodium hexametaphosphate (SHMP), is believed to have no physiological functions in mammalian cells. In this study, we explored the possible effects of SHMP on mammalian cells, using mouse oocytes, which are useful for observing various spatiotemporal intracellular changes. Fertilization-competent oocytes were isolated from the oviducts of superovulated mice and cultured in an SHMP-containing medium. In the absence of co-incubation with sperm, SHMP-treated oocytes frequently formed pronuclei and developed into two-cell embryos owing to the increase in calcium concentration in the cytoplasm. We discovered an intriguing role for SHMP as an initiator of calcium rise in mouse oocytes, presumably in a wide variety of mammalian cells.

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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

  • 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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