Updated on 2025/12/08

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写真a

 
Tomonari Hayama
 
Organization
YCU Medical Center Gynecology Associate Professor
Title
Associate Professor
Profile

H15年横浜市大卒、H17年産婦人科入局、生殖医療の研究をしています。

External link

Degree

  • 医学博士 ( 東大 )

Research Interests

  • 生殖医学

  • 顕微操作

  • 遺伝子治療

  • 生殖遺伝子治療

  • 卵巣腫瘍発生学

  • マイクロサージェリー

Research Areas

  • Life Science / Obstetrics and gynecology  / 卵巣胚細胞性腫瘍

  • Life Science / Obstetrics and gynecology  / 生殖医学

Education

  • The University of Tokyo   Faculty of Medicine

    2010.4 - 2014.3

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  • Yokohama City University

    1997.4 - 2003.3

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  • 神奈川県 私立聖光学院中・高等学校   少林寺拳法部所属 准拳士二段

    1991.4 - 1997.3

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Research History

  • 横浜市立大学市民総合医療センター   婦人科・生殖医療センター   准教授

    2024.4

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  • 横浜市立大学市民総合医療センター   婦人科・生殖医療センター   講師

    2020.4 - 2024.3

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  • 横浜市立大学市民総合医療センター   婦人科・生殖医療センター   助教

    2019.4 - 2020.3

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  • 済生会横浜市南部病院   産婦人科   副部長

    2018.12 - 2019.3

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  • Yokohama City University

    2018.4 - 2019.3

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  • オレゴン健康科学大学   胚遺伝子治療センター   研究員

    2015.9 - 2018.11

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  • オレゴン国立霊長類研   生殖発達科学分野   研究員

    2014.5 - 2018.11

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  • Yokohama City University   Assistant Professor

    2010.1 - 2010.3

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  • 横浜市大病院   産婦人科   指導診療医

    2009.3 - 2009.12

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  • Kanagawa Children's Medical Center

    2008.4 - 2009.3

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  • 横浜市民病院   産婦人科   診療医

    2006.4 - 2008.3

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  • Yokohama City University

    2005.4 - 2006.3

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  • Yokohama City University

    2003.5 - 2005.3

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Professional Memberships

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Committee Memberships

  • 日本生殖医学会   代議員  

    2024.4   

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    Committee type：Academic society

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  • 日本生殖医学会   生殖工学・再生医学SIG  

    2023.6   

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Papers

  • Single sperm karyotyping of testicular sperm in non-obstructive and obstructive azoospermia using next generation sequencing. Reviewed International journal

    Sumiko Sueyoshi, Akifumi Ijuin, Hiroe Ueno, Ai Miyakoshi, Haru Hamada, Misaki Toda, Naoki Tsuchiya, Miki Tanoshima, Mayuko Kurumizaka, Marina Saito, Yuki Oike, Kazumi Takeshima, Teppei Takeshima, Shinnosuke Kuroda, Yasushi Yumura, Shin Saito, Ryoko Asano, Taichi Mizushima, Etsuko Miyagi, Hideya Sakakibara, Hiroki Kurahashi, Akira Yanagihara, Mariko Murase, Tomonari Hayama

    PloS one   20 ( 12 )   e0338222   2025.12

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    The sperm of infertile men have higher rates of chromosomal abnormalities than those of fertile men. Miscarriage rate is also higher following testicular sperm extraction combined with intracytoplasmic sperm injection (TESE-ICSI). Sperm chromosomal abnormalities are assumed to be the cause of miscarriages. Previous testicular sperm karyotyping studies have only examined a few selected chromosomes using fluorescence in situ hybridization. The aim of this study was to provide a more detailed analysis of sperm karyotyping by analyzing all chromosomes using next-generation sequencing (NGS) in clinically usable testicular sperm. Sperm discarded after clinical use was collected for NGS. Additionally, sperm were individually collected by micromanipulation from patients with obstructive azoospermia (OA) and non-obstructive azoospermia (NOA) who underwent TESE-ICSI. For comparison, ejaculated sperm from control and balanced translocation (BT) carriers were examined. Karyotyping was performed on individual sperm cells using NGS. The number of normal and aberrant sperm was compared. Seventeen patients participated in this study: control (n = 4), BT (n = 3), OA (n = 5), and NOA (n = 5). Ten sperm samples per patient were analyzed. The total acquisition rate for single sperm karyotyping was 85% (145/170). Karyotyping of sperm from the BT group revealed sperm with unbalanced chromosomes derived from carrier translocations. Among the NOA group, 7/41 (17%) sperm samples exhibited aberrant karyotypes, whereas no aberrant sperm were identified in the control and OA groups. Individual differences were observed in the frequency of sperm chromosomal abnormalities among patients with NOA. In conclusion, sperm chromosomal abnormalities are frequently observed in patients with NOA even after sperm selection for clinical use. As the frequency of chromosomal abnormalities varies among patients with NOA, single sperm sequencing may help identify patients with NOA most likely to benefit from PGT-A.

    DOI： 10.1371/journal.pone.0338222

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  • Abnormal PAR1/2 Number Can Influence Effector T Cell Subsets in Turner Syndrome. Reviewed International journal

    Ai Miyakoshi, Sumiko Sueyoshi, Akifumi Ijuin, Haru Hamada, Mayuko Nishi, Shiori Tochihara, Marina Saito, Hiroe Ueno, Michi Kasai, Shin Saito, Ryoko Asano, Taichi Mizushima, Etsuko Miyagi, Mariko Murase, Miki Tanoshima, Hideya Sakakibara, Tomonari Hayama

    Molecular syndromology   1 - 11   2025.5

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    INTRODUCTION: Turner syndrome is a complicated gonadal insufficiency, infertility, and endocrine disease caused by the partial to complete loss of one X chromosome. Women with Turner syndrome have been reported to show altered effector T-cell subgroups; however, the relationship between T-cell subgroups and chromosome type remains unknown. METHODS: In this study, we investigated immune abnormalities and karyotypes of Turner syndrome. Using flowcytometry, we examined the T-cell subsets of 20 women with Turner syndrome and 23 women serving as controls (without recurrent pregnancy loss), between July 2021 and June 2022. Background data of the women with Turner syndrome were also collected. RESULTS: Significantly lower levels of helper T-cells 1 and 2 were observed in women with Turner syndrome than in the control group (4.5 ± 2.88 vs. 8.54 ± 4.45, p < 0.05, 0.56 ± 0.38 vs. 0.97 ± 0.48, p < 0.05, respectively). With respect to karyotypes, deletion of a specific region, pseudoautosomal region 2, which typically escapes X-inactivation, might influence regulatory T cells (Treg) levels as copy number of PAR2 and Treg rate were positively correlated (r = 0.76). CONCLUSION: Individuals with Turner syndrome showed an altered T-cell subset, which might be caused by the deletion of a specific part of the X chromosome, pseudoautosomal region 2. This finding suggests that women with Turner syndrome in a specific karyotype show altered T-cell subsets, and more cases are needed to determine whether these T-cell changes could influence pregnancy outcomes.

    DOI： 10.1159/000546378

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  • Effect of bisphosphonate and denosumab treatment on TBS in Japanese breast cancer patients with AIBL. Reviewed

    Emi Onuma, Shin Saito, Taku Tsuburai, Hiromi Yoshikata, Shoko Adachi, Shinya Yamamoto, Kazutaka Narui, Tomonari Hayama, Mariko Murase, Taichi Mizushima, Etsuko Miyagi, Hideya Sakakibara, Ryoko Asano

    Journal of bone and mineral metabolism   2024.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    INTRODUCTION: Bisphosphonates and denosumab increase bone mineral density (BMD) for osteoporosis treatment in patients with aromatase inhibitor-associated bone loss (AIBL). This study aimed to directly compare bisphosphonates with denosumab in treating patients with AIBL and to determine the effect of denosumab on the trabecular bone score (TBS). MATERIALS AND METHODS: Thirty-nine patients with AIBL receiving osteoporosis treatment (21 in the bisphosphonates group and 18 in the denosumab group) were retrospectively evaluated for changes in lumbar spine and femoral BMD, lumbar spine bone quality (assessed by TBS), and blood bone metabolic markers. The Mann-Whitney and Wilcoxon tests were used for statistical evaluation. RESULTS: After 24 months of treatment, the lumbar spine BMD change rate was 5.82 ± 1.10% with bisphosphonates and 10.49 ± 1.20% with denosumab, with the change rate of denosumab significantly increasing over that of bisphosphonates. The change rate in femoral BMD was 2.69 ± 1.16% with bisphosphonates and 2.95 ± 1.26% with denosumab, with no significant difference between the two groups. The rate of decrease in tartrate-resistant acid phosphatase isoform 5b was significantly higher in the denosumab group. The change rate in TBS at 24 months of treatment was 0.53 ± 1.26% in the bisphosphonates group and 1.08 ± 1.33% in the denosumab group, with no significant difference between the two groups. After 24 months, TBS remained stable. CONCLUSION: Both bisphosphonates and denosumab may increase BMD, improve bone metabolism, and inhibit bone quality loss in patients with AIBL.

    DOI： 10.1007/s00774-024-01542-2

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  • Use of AccuVein AV500 in differentiating veins from arteries during microsurgical varicocelectomy. Reviewed International journal

    Mitsuru Komeya, Tomoki Saito, Shinnosuke Kuroda, Haru Hamada, Ai Miyakoshi, Teppei Takeshima, Tomonari Hayama, Mariko Murase, Yasushi Yumura, Kazuhide Makiyama

    BJUI compass   4 ( 6 )   659 - 661   2023.11

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    DOI： 10.1002/bco2.271

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  • Mitochondrial DNA mutations can influence the post-implantation development of human mosaic embryos Reviewed

    Akifumi Ijuin, Hiroe Ueno, Tomonari Hayama, Shunsuke Miyai, Ai Miyakoshi, Haru Hamada, Sumiko Sueyoshi, Shiori Tochihara, Marina Saito, Haruka Hamanoue, Teppei Takeshima, Yasushi Yumura, Etsuko Miyagi, Hiroki Kurahashi, Hideya Sakakibara, Mariko Murase

    Frontiers in Cell and Developmental Biology   11   2023.8

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    Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

    Introduction: Several healthy euploid births have been reported following the transfer of mosaic embryos, including both euploid and aneuploid blastomeres. This has been attributed to a reduced number of aneuploid cells, as previously reported in mice, but remains poorly explored in humans. We hypothesized that mitochondrial function, one of the most critical factors for embryonic development, can influence human post-implantation embryonic development, including a decrease of aneuploid cells in mosaic embryos.

    Methods: To clarify the role of mitochondrial function, we biopsied multiple parts of each human embryo and observed the remaining embryos under in vitro culture as a model of post-implantation development (n = 27 embryos). Karyotyping, whole mitochondrial DNA (mtDNA) sequencing, and mtDNA copy number assays were performed on all pre- and post-culture samples.

    Results: The ratio of euploid embryos was significantly enhanced during in vitro culture, whereas the ratio of mosaic embryos was significantly reduced. Furthermore, post-culture euploid and culturable embryos had significantly few mtDNA mutations, although mtDNA copy numbers did not differ.

    Discussion: Our results indicate that aneuploid cells decrease in human embryos post-implantation, and mtDNA mutations might induce low mitochondrial function and influence the development of post-implantation embryos with not only aneuploidy but also euploidy. Analyzing the whole mtDNA mutation number may be a novel method for selecting a better mosaic embryo for transfer.

    DOI： 10.3389/fcell.2023.1215626

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  • The acceptance to germline gene therapy increased during COVID-19 pandemic among Japanese medical students. Reviewed International journal

    Akifumi Ijuin, Tomonari Hayama, Hideya Sakakibara

    The journal of obstetrics and gynaecology research   2022.3

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    DOI： 10.1111/jog.15246

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  • Horizontal mtDNA transfer between cells is common during mouse development. Reviewed International journal

    Nuria Marti Gutierrez, Aleksei Mikhalchenko, Hong Ma, Amy Koski, Ying Li, Crystal Van Dyken, Rebecca Tippner-Hedges, David Yoon, Dan Liang, Tomonari Hayama, David Battaglia, Eunju Kang, Yeonmi Lee, Anthony Paul Barnes, Paula Amato, Shoukhrat Mitalipov

    iScience   25 ( 3 )   103901 - 103901   2022.3

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    Cells transmit their genomes vertically to daughter cells during cell divisions. Here, we demonstrate the occurrence and extent of horizontal mitochondrial (mt)DNA acquisition between cells that are not in a parent-offspring relationship. Extensive single-cell sequencing from various tissues and organs of adult chimeric mice composed of cells carrying distinct mtDNA haplotypes showed that a substantial fraction of individual cardiomyocytes, neurons, glia, intestinal, and spleen cells captured donor mtDNA at high levels. In addition, chimeras composed of cells with wild-type and mutant mtDNA exhibited increased trafficking of wild-type mtDNA to mutant cells, suggesting that horizontal mtDNA transfer may be a compensatory mechanism to restore compromised mitochondrial function. These findings establish the groundwork for further investigations to identify mtDNA donor cells and mechanisms of transfer that could be critical to the development of novel gene therapies.

    DOI： 10.1016/j.isci.2022.103901

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  • Outcomes of the study of intracytoplasmic sperm injection (ICSI) and sperm motility with microdissection testicular sperm extraction Reviewed

    Yuuka Arai, Hiroe Ueno, Mizuki Yamamoto, Haruna Izumi, Kazumi Takeshima, Tomonari Hayama, Hideya Sakakibara, Yasushi Yumura, Etsuko Miyagi, Mariko Murase

    Asian Journal of Andrology   24 ( 2 )   221 - 221   2022.3

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    Publishing type：Research paper (scientific journal)   Publisher：Medknow  

    DOI： 10.4103/aja202152

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  • Fertility preservation immediately after therapeutic abortion results in multiple normal follicular growth with the absence of mature oocytes due to early luteinization: a case report and literature review. Reviewed International journal

    Haru Hamada, Tomonari Hayama, Akifumi Ijuin, Ai Miyakoshi, Michi Kasai, Shiori Tochihara, Marina Saito, Mayuko Nishi, Hiroe Ueno, Mizuki Yamamoto, Mitsuru Komeya, Yasushi Yumura, Hideya Sakakibara, Etsuko Miyagi, Mariko Murase

    Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology   37 ( 11 )   1 - 4   2021.7

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    Cancer therapy has priority over fertility preservation. The time available for fertility preservation in patients with cancer is often very limited and depends on the condition of the underlying disease. This case report presents the results of two rounds of controlled ovarian stimulations (COSs) performed after an induced abortion. The patient had mixed phenotype acute leukemia diagnosed during early pregnancy and underwent a surgical abortion, followed by ovarian stimulation using urinary follicle-stimulating hormone (uFSH) and gonadotropin-releasing hormone (GnRH) agonists. Oocyte retrieval was subsequently performed for oocyte cryopreservation. Despite good hormonal and ultrasonic follicular growth, no oocytes were obtained. During a second COS performed at a low human chorionic gonadotropin (hCG) level (less than 100 IU/L), several mature oocytes were obtained, suggesting that higher hCG levels during COS induce the absence of mature oocytes during normal follicular growth. It is recommended to start COS post-abortion after confirming a low hCG level while considering the timing of cancer treatment.

    DOI： 10.1080/09513590.2021.1950135

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  • Deleterious mtDNA mutations are common in mature oocytes. Reviewed International journal

    Hong Ma, Tomonari Hayama, Crystal Van Dyken, Hayley Darby, Amy Koski, Yeonmi Lee, Nuria Marti Gutierrez, Satsuki Yamada, Ying Li, Michael Andrews, Riffat Ahmed, Dan Liang, Thanasup Gonmanee, Eunju Kang, Mohammed Nasser, Beth Kempton, John Brigande, Trevor J McGill, Andre Terzic, Paula Amato, Shoukhrat Mitalipov

    Biology of reproduction   102 ( 3 )   607 - 619   2020.3

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    Heritable mitochondrial DNA (mtDNA) mutations are common, yet only a few recurring pathogenic mtDNA variants account for the majority of known familial cases in humans. Purifying selection in the female germline is thought to be responsible for the elimination of most harmful mtDNA mutations during oogenesis. Here we show that deleterious mtDNA mutations are abundant in ovulated mature mouse oocytes and preimplantation embryos recovered from PolG mutator females but not in their live offspring. This implies that purifying selection acts not in the maternal germline per se, but during post-implantation development. We further show that oocyte mtDNA mutations can be captured and stably maintained in embryonic stem cells and then reintroduced into chimeras, thereby allowing examination of the effects of specific mutations on fetal and postnatal development.

    DOI： 10.1093/biolre/ioz202

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  • Author Correction: Mitochondrial replacement in human oocytes carrying pathogenic mitochondrial DNA mutations. International journal

    Eunju Kang, Jun Wu, Nuria Marti Gutierrez, Amy Koski, Rebecca Tippner-Hedges, Karen Agaronyan, Aida Platero-Luengo, Paloma Martinez-Redondo, Hong Ma, Yeonmi Lee, Tomonari Hayama, Crystal Van Dyken, Xinjian Wang, Shiyu Luo, Riffat Ahmed, Ying Li, Dongmei Ji, Refik Kayali, Cengiz Cinnioglu, Susan Olson, Jeffrey Jensen, David Battaglia, David Lee, Diana Wu, Taosheng Huang, Don P Wolf, Dmitry Temiakov, Juan Carlos Izpisua Belmonte, Paula Amato, Shoukhrat Mitalipov

    Nature   567 ( 7747 )   E5-E9   2019.3

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    Change history In this Letter, there are several errors regarding the assignments of mtDNA haplotypes for a subset of egg donors from our study. These errors have not been corrected online.

    DOI： 10.1038/s41586-019-0876-1

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  • Generation of Vascular Endothelial Cells and Hematopoietic Cells by Blastocyst Complementation. Reviewed International journal

    Sanae Hamanaka, Ayumi Umino, Hideyuki Sato, Tomonari Hayama, Ayaka Yanagida, Naoaki Mizuno, Toshihiro Kobayashi, Mariko Kasai, Fabian Patrik Suchy, Satoshi Yamazaki, Hideki Masaki, Tomoyuki Yamaguchi, Hiromitsu Nakauchi

    Stem cell reports   11 ( 4 )   988 - 997   2018.10

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    In the case of organ transplantation accompanied by vascular anastomosis, major histocompatibility complex mismatched vascular endothelial cells become a target for graft rejection. Production of a rejection-free, transplantable organ, therefore, requires simultaneous generation of vascular endothelial cells within the organ. To generate pluripotent stem cell (PSC)-derived vascular endothelial cells, we performed blastocyst complementation with a vascular endothelial growth factor receptor-2 homozygous mutant blastocyst. This mutation is embryonic lethal at embryonic (E) day 8.5-9.5 due to an early defect in endothelial and hematopoietic cells. The Flk-1 homozygous knockout chimeric mice survived to adulthood for over 1 year without any abnormality, and all vascular endothelial cells and hematopoietic cells were derived from the injected PSCs. This approach could be used in conjunction with other gene knockouts which induce organ deficiency to produce a rejection-free, transplantable organ in which all the organ's cells and vasculature are PSC derived.

    DOI： 10.1016/j.stemcr.2018.08.015

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  • Large deletions induced by Cas9 cleavage Reply Reviewed

    Ma Hong, Marti-Gutierrez Nuria, Park Sang-Wook, Wu Jun, Hayama Tomonari, Darby Hayley, Van Dyken Crystal, Li Ying, Koski Amy, Liang Dan, Suzuki Keiichiro, Gu Ying, Gong Jianhui, Xu Xun, Ahmed Riffat, Lee Yeonmi, Kang Eunju, Ji Dongmei, Park A-Reum, Kim Daesik, Kim Sang-Tae, Heitner Stephen B, Battaglia David, Krieg Sacha A, Lee David M, Wu Diana H, Wolf Don P, Amato Paula, Kaul Sanjiv, Belmonte Juan, Carlos Izpisua, Kim Jin-Soo, Mitalipov Shoukhrat

    NATURE   560 ( 7717 )   E10 - E23   2018.8

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  • Germline and somatic mtDNA mutations in mouse aging. Reviewed International journal

    Hong Ma, Yeonmi Lee, Tomonari Hayama, Crystal Van Dyken, Nuria Marti-Gutierrez, Ying Li, Riffat Ahmed, Amy Koski, Eunju Kang, Hayley Darby, Thanasup Gonmanee, Younjung Park, Don P Wolf, Chong Jai Kim, Shoukhrat Mitalipov

    PloS one   13 ( 7 )   e0201304   2018

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    The accumulation of acquired mitochondrial genome (mtDNA) mutations with aging in somatic cells has been implicated in mitochondrial dysfunction and linked to age-onset diseases in humans. Here, we asked if somatic mtDNA mutations are also associated with aging in the mouse. MtDNA integrity in multiple organs and tissues in young and old (2-34 months) wild type (wt) mice was investigated by whole genome sequencing. Remarkably, no acquired somatic mutations were detected in tested tissues. However, we identified several non-synonymous germline mtDNA variants whose heteroplasmy levels (ratio of normal to mutant mtDNA) increased significantly with aging suggesting clonal expansion of inherited mtDNA mutations. Polg mutator mice, a model for premature aging, exhibited both germline and somatic mtDNA mutations whose numbers and heteroplasmy levels increased significantly with age implicating involvement in premature aging. Our results suggest that, in contrast to humans, acquired somatic mtDNA mutations do not accompany the aging process in wt mice.

    DOI： 10.1371/journal.pone.0201304

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  • Mitochondrial genome inheritance and replacement in the human germline. Invited Reviewed International journal

    Don P Wolf, Tomonari Hayama, Shoukhrat Mitalipov

    The EMBO journal   36 ( 17 )   2659 - 2659   2017.9

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.15252/embj.201797843

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  • Correction of a pathogenic gene mutation in human embryos. Reviewed International journal

    Hong Ma, Nuria Marti-Gutierrez, Sang-Wook Park, Jun Wu, Yeonmi Lee, Keiichiro Suzuki, Amy Koski, Dongmei Ji, Tomonari Hayama, Riffat Ahmed, Hayley Darby, Crystal Van Dyken, Ying Li, Eunju Kang, A-Reum Park, Daesik Kim, Sang-Tae Kim, Jianhui Gong, Ying Gu, Xun Xu, David Battaglia, Sacha A Krieg, David M Lee, Diana H Wu, Don P Wolf, Stephen B Heitner, Juan Carlos Izpisua Belmonte, Paula Amato, Jin-Soo Kim, Sanjiv Kaul, Shoukhrat Mitalipov

    Nature   548 ( 7668 )   413 - 419   2017.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/nature23305

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  • Mitochondrial genome inheritance and replacement in the human germline. Reviewed International journal

    Don P Wolf, Tomonari Hayama, Shoukhrat Mitalipov

    The EMBO journal   36 ( 15 )   2177 - 2181   2017.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.15252/embj.201797606

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  • Functional Human Oocytes Generated by Transfer of Polar Body Genomes. Reviewed International journal

    Hong Ma, Ryan C O'Neil, Nuria Marti Gutierrez, Manoj Hariharan, Zhuzhu Z Zhang, Yupeng He, Cengiz Cinnioglu, Refik Kayali, Eunju Kang, Yeonmi Lee, Tomonari Hayama, Amy Koski, Joseph Nery, Rosa Castanon, Rebecca Tippner-Hedges, Riffat Ahmed, Crystal Van Dyken, Ying Li, Susan Olson, David Battaglia, David M Lee, Diana H Wu, Paula Amato, Don P Wolf, Joseph R Ecker, Shoukhrat Mitalipov

    Cell stem cell   20 ( 1 )   112 - 119   2017.1

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.stem.2016.10.001

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  • Concise Review: Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer: A Horse in the Race? Invited Reviewed International journal

    Don P Wolf, Robert Morey, Eunju Kang, Hong Ma, Tomonari Hayama, Louise C Laurent, Shoukhrat Mitalipov

    Stem cells (Dayton, Ohio)   35 ( 1 )   26 - 34   2017.1

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    DOI： 10.1002/stem.2496

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  • Mitochondrial replacement in human oocytes carrying pathogenic mitochondrial DNA mutations. Reviewed International journal

    Eunju Kang, Jun Wu, Nuria Marti Gutierrez, Amy Koski, Rebecca Tippner-Hedges, Karen Agaronyan, Aida Platero-Luengo, Paloma Martinez-Redondo, Hong Ma, Yeonmi Lee, Tomonari Hayama, Crystal Van Dyken, Xinjian Wang, Shiyu Luo, Riffat Ahmed, Ying Li, Dongmei Ji, Refik Kayali, Cengiz Cinnioglu, Susan Olson, Jeffrey Jensen, David Battaglia, David Lee, Diana Wu, Taosheng Huang, Don P Wolf, Dmitry Temiakov, Juan Carlos Izpisua Belmonte, Paula Amato, Shoukhrat Mitalipov

    Nature   540 ( 7632 )   270 - 275   2016.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/nature20592

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  • Incompatibility between Nuclear and Mitochondrial Genomes Contributes to an Interspecies Reproductive Barrier. Reviewed International journal

    Hong Ma, Nuria Marti Gutierrez, Robert Morey, Crystal Van Dyken, Eunju Kang, Tomonari Hayama, Yeonmi Lee, Ying Li, Rebecca Tippner-Hedges, Don P Wolf, Louise C Laurent, Shoukhrat Mitalipov

    Cell metabolism   24 ( 2 )   283 - 94   2016.8

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    DOI： 10.1016/j.cmet.2016.06.012

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  • Practical selection methods for rat and mouse round spermatids without DNA staining by flow cytometric cell sorting. Reviewed International journal

    Tomonari Hayama, Tomoyuki Yamaguchi, Megumi Kato-Itoh, Yumiko Ishii, Naoaki Mizuno, Ayumi Umino, Hideyuki Sato, Makoto Sanbo, Sanae Hamanaka, Hideki Masaki, Masumi Hirabayashi, Hiromitsu Nakauchi

    Molecular reproduction and development   83 ( 6 )   488 - 96   2016.6

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1002/mrd.22644

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  • Age-Related Accumulation of Somatic Mitochondrial DNA Mutations in Adult-Derived Human iPSCs. Reviewed International journal

    Eunju Kang, Xinjian Wang, Rebecca Tippner-Hedges, Hong Ma, Clifford D L Folmes, Nuria Marti Gutierrez, Yeonmi Lee, Crystal Van Dyken, Riffat Ahmed, Ying Li, Amy Koski, Tomonari Hayama, Shiyu Luo, Cary O Harding, Paula Amato, Jeffrey Jensen, David Battaglia, David Lee, Diana Wu, Andre Terzic, Don P Wolf, Taosheng Huang, Shoukhrat Mitalipov

    Cell stem cell   18 ( 5 )   625 - 36   2016.5

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    DOI： 10.1016/j.stem.2016.02.005

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  • A Safeguard System for Induced Pluripotent Stem Cell-Derived Rejuvenated T Cell Therapy. Reviewed International journal

    Miki Ando, Toshinobu Nishimura, Satoshi Yamazaki, Tomoyuki Yamaguchi, Ai Kawana-Tachikawa, Tomonari Hayama, Yusuke Nakauchi, Jun Ando, Yasunori Ota, Satoshi Takahashi, Ken Nishimura, Manami Ohtaka, Mahito Nakanishi, John J Miles, Scott R Burrows, Malcolm K Brenner, Hiromitsu Nakauchi

    Stem cell reports   5 ( 4 )   597 - 608   2015.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.stemcr.2015.07.011

    Web of Science

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  • Metabolic rescue in pluripotent cells from patients with mtDNA disease. Reviewed International journal

    Hong Ma, Clifford D L Folmes, Jun Wu, Robert Morey, Sergio Mora-Castilla, Alejandro Ocampo, Li Ma, Joanna Poulton, Xinjian Wang, Riffat Ahmed, Eunju Kang, Yeonmi Lee, Tomonari Hayama, Ying Li, Crystal Van Dyken, Nuria Marti Gutierrez, Rebecca Tippner-Hedges, Amy Koski, Nargiz Mitalipov, Paula Amato, Don P Wolf, Taosheng Huang, Andre Terzic, Louise C Laurent, Juan Carlos Izpisua Belmonte, Shoukhrat Mitalipov

    Nature   524 ( 7564 )   234 - 8   2015.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/nature14546

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  • Successful reprogramming of epiblast stem cells by blocking nuclear localization of β-catenin. Reviewed International journal

    Hideyuki Murayama, Hideki Masaki, Hideyuki Sato, Tomonari Hayama, Tomoyuki Yamaguchi, Hiromitsu Nakauchi

    Stem cell reports   4 ( 1 )   103 - 113   2015.1

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.stemcr.2014.12.003

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  • Generation of mouse functional oocytes in rat by xeno-ectopic transplantation of primordial germ cells. Reviewed International journal

    Tomonari Hayama, Tomoyuki Yamaguchi, Megumi Kato-Itoh, Sanae Hamanaka, Mami Kawarai, Makoto Sanbo, Chihiro Tamura, Youn-Su Lee, Ayaka Yanagida, Hideyuki Murayama, Naoaki Mizuno, Ayumi Umino, Hideyuki Sato, Satoshi Yamazaki, Hideki Masaki, Toshihiro Kobayashi, Masumi Hirabayashi, Hiromitsu Nakauchi

    Biology of reproduction   91 ( 4 )   89 - 89   2014.10

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1095/biolreprod.114.121640

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  • Development of an all-in-one inducible lentiviral vector for gene specific analysis of reprogramming. Reviewed International journal

    Tomoyuki Yamaguchi, Sanae Hamanaka, Akihide Kamiya, Motohito Okabe, Mami Kawarai, Yukiko Wakiyama, Ayumi Umino, Tomonari Hayama, Hideyuki Sato, Youn-Su Lee, Megumi Kato-Itoh, Hideki Masaki, Toshihiro Kobayashi, Satoshi Yamazaki, Hiromitsu Nakauchi

    PloS one   7 ( 7 )   e41007   2012

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1371/journal.pone.0041007

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Books

  • 受精とその障害

    柴原, 浩章, 柳田, 薫（6.良好精子回収法／葉山智工・上野寛枝）

    中外医学社  2022.11  （ ISBN:9784498160422 ）

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    Total pages：v, 153p   Language：Japanese  

    CiNii Books

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MISC

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Presentations

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Industrial property rights

  • 妊孕性を判定するためのバイオマーカー及びそれを用いた判定方法

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    Application no：特願2022-169943  Date applied：2022.10

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Awards

  • JSOG Congress Award

    2023.5   Inappropriate Reprogramming Induce Carcinogenesis of Ovarian Embryonal Carcinoma in Rodent Ovary

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  • The Basic Science Award for poster presentation

    2019.6   Eshre2019 35th Anual Meeting   Pathogenic mtDNA mutations are abundant in oocytes but eliminated during fetal development

    Tomonari Hayama

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  • JSOG Congress Encouragement Award

    2019.4   Pathogenic mtDNA mutations are common in oocytes but eliminated in post-implantation development due to fetal demise

    Tomonari Hayama

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  • Best Poster Award

    2017.10   6th Annual Gene Therapy Symposium   Negative selection for deleterious mtDNA mutations in the mouse germline

    Tomonari Hayama

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  • 学会ボランティア活動賞

    2011.8   日本産婦人科学会   東北地方太平洋沖地震の被災地、石巻市に於いて産婦人科医療の支援に献身的な貢献

    葉山 智工

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Research Projects

  • 着床期の胚・子宮内膜相互作用をコントロールする新規分子の解析

    Grant number：22K07920  2022.4 - 2025.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    村瀬 真理子, 上野 寛枝, 葉山 智工, 木村 弥生

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    Grant amount：\4290000 （ Direct Cost: \3300000 、 Indirect Cost：\990000 ）

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  • 染色体異常モザイク胚から健常児が生まれるのはなぜか？

    Grant number：21K09474  2021.4 - 2024.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    宮腰 藍衣, 上野 寛枝, 葉山 智工, 村瀬 真理子, 浜之上 はるか

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    Grant amount：\4290000 （ Direct Cost: \3300000 、 Indirect Cost：\990000 ）

    本研究の目的は染色体異常モザイク胚における染色体異常細胞・正常細胞構成の部位による違いを明らかにし、生検後残った細胞を培養し、経時的に追跡して異常細胞が発生過程で淘汰されるのか否か、その経過とミトコンドリアの変化を評価することである。その目的実現のために下記のように研究計画ごとに状況を報告する。
    ①胚生検：一つの胚盤胞から複数個所の生検を行う⇒提供検体がさらに収集されており順調に進行している。②染色体・ミトコンドリア解析：生検検体に対して次世代シークエンサ・real time PCRを用いて核型の同定・ミトコンドリアDNAコピー数解析・ミトコンドリアDNA変異解析を行う⇒現在収集されている生検検体に対するの解析は終了しており順調に進行している。③生検後の胚培養⇒上記同様に順調に進行しており培養後の細胞からDNA検体を収集している。④染色体解析結果と培養可能期間の比較：培養継続可能な胚において染色体・ミトコンドリア解析結果を比較する⇒培養可能期間によって長期培養可能胚と不可能胚
    に分け解析結果と培養状況の比較が順調に進行している。⑤胚培養中の細胞生検：生検後培養の経過において増殖した細胞塊を回収しそれらに対して染色体・ミトコンドリア解析を行うことで培養前後における変化を比較する⇒培養を行った全胚に関して培養経過中の細胞を回収しておりそれらに対する染色体・ミトコンドリア解析は順調に進行している。
    解析は順調に進行しており現在は、その結果をまとめ評価を行っている。それとともに更なる検体の収集に努めている。

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  • リプログラマブル動物卵巣を用いた卵巣胎児性癌発生モデルの開発、発病トリガーの解明

    Grant number：20K18169  2020.4 - 2023.3

    日本学術振興会  科学研究費助成事業  若手研究

    葉山 智工

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    Grant amount：\4030000 （ Direct Cost: \3100000 、 Indirect Cost：\930000 ）

    本研究の研究実施計画に沿って詳述する。
    ・胎児性癌の発生原因は卵巣組織内の不適切なリプログラミングである証明：モデル動物内にこの腫瘍を発病させる実験に成功したので、さまざまな切り口で腫瘍発生を観察した。生殖細胞が腫瘍化する瞬間をモデル動物臓器内で前方視的に捉えて、胎児性癌の発生原因と、不適切な卵巣組織内でのリプログラミングの関係を示唆できた。
    ・胎児性癌細胞の発癌初期の腫瘍形成の場“ニッチ（ゆりかご）”の解明：モデル動物で遺伝学的トレースマーカーを用いて経時的に卵巣組織内で生殖細胞が原因となるのかが明らかにされた。メカニズムの解明を成し得た。
    ・胎児性癌の腫瘍形成ニッチでの遺伝子発現変化とエピジェネティック変化の解明：発癌前の組織と発癌後の組織の遺伝子発現を網羅的に解析することにより、発癌のキーとなる遺伝子群は明らかにされた。しかし、残念ながら完全にキーとなる遺伝子は単離されなかったが、遺伝子群に関する示唆を得た。
    ・ヒト胎児性癌患者さん培養細胞での後方視的検証とマーカー候補探索：ヒト胎児性癌培養細胞とげっ歯類モデルの遺伝子発現比較を行い発癌現象の高い類似性が、明らかにされた。上記までの成果で原著論文を執筆、投稿準備中である。
    ・抗がん剤の効果を調べる胎児性癌ラットモデルの作成：ヒト癌と同様に転移や病状の評価が可能なラットモデルで発症させたラット個体を用いて胎児性癌の原発巣・転移巣に対する抗がん剤の効果を調べる応用は今後順次行う予定である。

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Teaching Experience

  • Reproductive Medicine

    2020 Institution：Yokohama City University

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  • Bioethics Reproductive Bioethics

    2020 Institution：Yokohama City University

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