Updated on 2026/07/29

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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

  • 顕微操作

  • 遺伝子治療

  • 生殖遺伝子治療

  • 卵巣腫瘍発生学

  • 生殖医学

Research Areas

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

  • Life Science / Obstetrics and gynecology  / 生殖医学

  • Life Science / Developmental biology  / 胚性幹細胞

Education

  • The University of Tokyo   Faculty of Medicine

    2010.4 - 2014.3

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  • Yokohama City University   School of Medicine

    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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  • Yokohama National University   College of Education

    1985.4 - 1991.3

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Research History

  • Yokohama City University

    2025.4

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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   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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  • Yokohama City University

    2019.4

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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   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   第72回日本生殖医学会学術講演会・総会 副会長  

    2026.4 - 2027.11   

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  • 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 委員  

    2023.6   

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Papers

  • Predicting recurrence risk of Leigh syndrome using prenatal mtDNA heteroplasmy assessment

    Maria Shishimorova, Hong Ma, Amy Koski, Crystal Van Dyken, Nuria Marti Gutierrez, Daniel Frana, Ying Li, Daniel Eyberg, Sergei Tevkin, Tomonari Hayama, Eunju Kang, Paula Amato, Kevin Havlin, Christopher Goodier, Roger Newman, Sally Shields, Shoukhrat Mitalipov

    Mitochondrion   2026.9

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    Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.mito.2026.102165

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  • Intraoperative Visualization of the Left Common Iliac Vein Using Indocyanine Green via Lower-Extremity Injection During Laparoscopic Sacral Colpopexy

    Shizuka Sakurai, Go Hirata, Megumi Yamasaki, Yui Noguchi, Mai Tanaka, Shin Saito, Tomonari Hayama, Yasuyo Maruyama, Mariko Murase, Etsuko Miyagi, Ryoko Asano

    Journal of Minimally Invasive Gynecology   2026.7

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    Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.jmig.2026.07.027

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  • Spontaneous miscarriage after intracytoplasmic sperm injection with frozen sperm of patients with testicular germ cell tumour. International journal

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

    BJU international   2026.6

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

    OBJECTIVE: To clarify the impact of chromosomal aberrations on the offspring of patients with testicular germ cell tumour (TGCT) by evaluating the outcomes of intracytoplasmic sperm injection (ICSI). PATIENTS AND METHODS: Under the ethical review of Yokohama City University, 12 patients with TGCT and 25 with non-TGCT cancer who had cryopreserved sperm for ICSI for fertility preservation between 1 April 2014 and 31 March 2023 were enrolled. For 198 oocytes from the TGCT group, 480 oocytes from the non-TGCT group, fertilisation, embryo viability, pregnancy, and spontaneous miscarriage rates were examined. RESULTS: Females who received ICSI from patients with TGCT showed a significantly higher spontaneous miscarriage rate than those who received ICSI from patients with non-TGCT cancer (43.8% vs 9.1%, respectively, P < 0.05), with no significant between-group difference in the pregnancy rate. In the TGCT group, three cases of recurrent pregnancy loss and recurrent implantation failure were reported. The high spontaneous miscarriage rate in the TGCT group can be attributed to chromosomal abnormalities or DNA fragmentation in the sperm of patients with TGCT. CONCLUSION: Natural conception may be an option for patients who have completed TGCT treatment and have adequate sperm. However, when semen parameters do not recover sufficiently, assisted reproductive technologies may be considered, including, where possible, the use of post-treatment sperm not affected by TGCT rather than pre-treatment sperm collected during tumour-bearing state. In selected cases, pre-implantation genetic testing for aneuploidy may also be considered.

    DOI： 10.1111/bju.70332

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

    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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    Language：English  

    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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  • 腹腔鏡下副角子宮切除後に体外受精により妊娠・分娩に至った1例 Reviewed

    宮腰 藍衣, 伊集院 昌郁, 葉山 智工, 村瀬 真理子, 榊原 秀也, 宮城 悦子

    神奈川産科婦人科学会誌   57 ( 1 )   63 - 68   2020.9

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    Language：Japanese   Publisher：神奈川産科婦人科学会  

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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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  • 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. Invited 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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    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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    DOI： 10.1016/j.stemcr.2015.07.011

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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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    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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    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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    DOI： 10.1371/journal.pone.0041007

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  • A case of Benign Metastasizing Leiomyoma with bone metastasis Reviewed

    HAYAMA Tomonari, MIZUSHIMA Taichi, KATO Yuki, AOKI Shigeru, ASAI SATO Mikiko, ANDO Noriko, HAYASHI Hiroyuki, SHIGETA Hiroyuki

    日本婦人科腫瘍学会雑誌 = The journal of the Japan Society of Gynecologic Oncology   29 ( 2 )   323 - 328   2011.4

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    CiNii Books

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  • 甲状腺クリーゼを合併した広汎性発達障害の1例

    須田 顕, 長谷川 花, 山田 康弘, 鈴木 東洋, 葉山 智工, 小田原 俊成

    神奈川県精神医学会雑誌   33 ( 1 )   67 - 67   2006.1

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  • 子宮摘出が有効であった,比較的高齢女性に認めた侵入奇胎の1症例 Reviewed

    葉山 智工, 倉澤 健太郎, 井畑 穰, 横田 奈朋, 神田 義明, 佐治 晴哉, 吉田 浩, 佐藤 美紀子, 杉浦 賢, 宮城 悦子, 平原 史樹

    日本産科婦人科学会神奈川地方部会会誌   42 ( 2 )   145 - 147   2006.1

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    Authorship：Lead author   Language：Japanese   Publisher：神奈川産科婦人科学会  

    46歳0経産婦.患者は不正性器出血を主訴に近医を受診,絨毛性疾患を疑われ,著者らの施設へ紹介入院となった.入院時,尿中hCG,血中hCG-βの上昇を認め,子宮頸部/内膜細胞診はclassI/IIIであった.経腟超音波では子宮内に中〜高輝度の腫瘍を認めた.絨毛癌診断スコアは1点であったが,絨毛癌に移行する可能性が高かったため,手術を予定した.入院6日目に下腹部痛,出血とともに内容物が一部排出され,排出物は胞状奇胎と診断された.high risk群の侵入奇胎が疑われ,入院7日目に腹式単純子宮全摘術および両側付属器摘出術を行った.その結果,術後病理診断は侵入奇胎で,遺伝子診断では雄性発生2精子受精疑いであった.術後経過は良好であった

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  • 生殖医療の先端技術：胚遺伝子治療の未来?顕微操作での研究技術をもつ産婦人科医の可能性?

    葉山 智工

    産婦人科の実際 Vol.74 No.9 特集 産婦人科の未来予想図?これから必要な技術、資格について  2025.9 

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  • 特集3 不妊治療 Part2 不妊治療の費用

    葉山智工

    エキスパートナース Vol.40 No.1  2024.1 

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  • 【ミトコンドリア 疾患治療の新時代】生殖補助技術を用いた受精胚でのミトコンドリア病の根本治療戦略と展望

    葉山智工

    実験医学増刊号 Vol.41 No.5  2023.3 

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  • 6.良好精子回収法

    葉山智工, 上野寛枝, 柴原浩章, 編集主幹, 柳田 薫 企画編集（6.良好精子回収法／葉山智工・上野寛枝）

    中外医学社 生殖医療フロントラインMOOK2 受精とその障害  2022.11  （ ISBN:9784498160422 ）

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    Total pages：v, 153p   Language：Japanese  

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  • 不妊治療の保険適用拡大の意義－薬局薬剤師への影響を含めて

    葉山智工, 倉澤健太郎

    調剤と情報、Vol.28、No.13 2192-2197  2022.10 

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  • 【特集 受精と胚発生をめぐる話題】ミトコンドリア遺伝子異常とその治療

    葉山智工

    (株)メディカルレビュー社 HORMONE FRONTIER IN GYNECOLOGY 29(1) 37-42  2022.3 

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  • マウス胎児由来iPS細胞をEB法で分化誘導し2種類の生殖細胞マーカーで生殖細胞を染色した図

    葉山智工, 日本再生医療学会, 山中 伸弥, 中内 啓光

    朝倉書店 再生医療叢書 1幹細胞 口絵  2012.10  （ ISBN:9784254360714 ）

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  • 【ニューテクノロジー 明日の生殖医学研究に向けて】 iPS細胞研究の現状と生殖細胞研究との関連

    葉山 智工, 山口 智之, 中内 啓光

    (株)メディカルレビュー社 HORMONE FRONTIER IN GYNECOLOGY 18(1) 69-78  2011.3 

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  • VARIETY OF SPERMATOGENESIS IN INFERTILE MEN WITH BALANCED RECIPROCAL CHROMO-SOME TRANSLOCATION: A CASE SERIES.

    Shinnosuke Kuroda, Teppei Takeshima, Tomonari Hayama, Yasushi Yumura

    FERTILITY AND STERILITY   124 ( 6 )   2025.12

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  • 神奈川県における妊孕性温存ネットワーク「かなおふネット」実績報告 男性側

    湯村 寧, 竹島 徹平, 黒田 晋之介, 洞下 由記, 高江 正道, 村瀬 真理子, 葉山 智工, 榊原 秀也, 鈴木 直, 宮城 悦子

    日本生殖医学会雑誌   69 ( 4 )   480 - 480   2024.10

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  • 当院における男性不妊症患者に対する遺伝学的検査の検討 生殖医療センター開設からの変遷

    黒田 晋之介, 下木原 航太, 竹島 徹平, 齋藤 智樹, 苅部 樹里衣, 葉山 智工, 村瀬 真理子, 湯村 寧

    日本生殖医学会雑誌   69 ( 4 )   426 - 426   2024.10

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  • 不妊を主訴としたXX maleの4例

    下木原 航太, 黒田 晋之介, 竹島 徹平, 葉山 智工, 村瀬 真理子, 湯村 寧

    日本生殖医学会雑誌   69 ( 4 )   431 - 431   2024.10

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  • 調節卵巣刺激周期における3D超音波による卵胞計測

    濱田春, 土屋尚輝, 末吉寿実鼓, 戸田美咲, 伊集院昌郁, 宮腰藍衣, 葉山智工, 胡桃坂真由子, 栃原しおり, 齋藤満里奈, 大池有紀, 上野寛枝, 下木原航太, 黒田晋之介, 竹島徹平, 湯村寧, 榊原秀也, 宮城悦子, 村瀬真理子

    日本生殖医学会雑誌   69 ( 4 )   2024

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  • 卵巣明細胞癌における妊孕性温存症例2例

    土屋尚輝, 末吉寿実鼓, 戸田美咲, 濱田春, 伊集院昌郁, 宮腰藍衣, 葉山智工, 胡桃坂真由子, 大池有紀, 栃原しおり, 齋藤満里奈, 上野寛枝, 下木原航太, 黒田晋之介, 竹島徹平, 湯村寧, 宮城悦子, 榊原秀也, 村瀬真理子

    日本生殖医学会雑誌   69 ( 4 )   2024

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  • 当院におけるクラインフェルター症候群のART成績

    戸田美咲, 土屋尚輝, 末吉寿実鼓, 濱田春, 伊集院昌郁, 宮腰藍衣, 葉山智工, 胡桃坂真由子, 大池有紀, 栃原しおり, 齋藤満里奈, 上野寛枝, 下木原航太, 黒田晋之介, 竹島徹平, 湯村寧, 榊原秀也, 宮城悦子, 村瀬真理子

    日本生殖医学会雑誌   69 ( 4 )   2024

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  • 培養液中cell-free DNAによる非侵襲的胚ミトコンドリアDNA変異解析

    伊集院昌郁, 末吉寿実鼓, 上野寛枝, 葉山智工, 土屋尚輝, 宮腰藍衣, 戸田美咲, 濱田春, 胡桃坂真由子, 大池有紀, 栃原しおり, 齋藤満里奈, 下木原航太, 黒田晋之介, 竹島徹平, 湯村寧, 宮城悦子, 榊原秀也, 村瀬真理子

    日本生殖医学会雑誌   69 ( 4 )   2024

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  • 非閉塞性無精子症に対する外科的精子採取アプリケーションの開発

    竹島徹平, 齋藤智樹, 苅部樹里衣, 黒田晋之介, 古目谷暢, 栃原しおり, 齋藤満里奈, 上野寛枝, 戸田美咲, 末吉寿実鼓, 濱田春, 伊集院昌郁, 宮腰藍衣, 葉山智工, 村瀬真理子, 湯村寧

    日本生殖医学会雑誌   69 ( 4 )   2024

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  • 妊孕性温存目的に子宮内膜癌MPA療法を受けた患者の妊娠転帰と再発頻度

    葉山智工, 土屋尚輝, 末吉寿実鼓, 伊集院昌郁, 葉山智工, 土屋尚輝, 末吉寿実鼓, 伊集院昌郁, 戸田美咲, 濱田春, 胡桃坂真由子, 大池有紀, 栃原しおり, 齋藤満里奈, 上野寛枝, 下木原航太, 黒田晋之介, 竹島徹平, 湯村寧, 宮城悦子, 榊原秀也, 村瀬真理子

    日本生殖医学会雑誌   69 ( 4 )   2024

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  • 胚培養時に精液由来の細菌増殖を認めた一例

    戸田美咲, 末吉寿実鼓, 浜田春, 伊集院昌郁, 宮腰藍衣, 葉山智工, 榊原秀也, 村瀬真理子

    神奈川医学会雑誌   51 ( 2 )   2024

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  • 紡錘体様式は多前核出現率と胚発生に影響する

    上野寛枝, 齋藤満里奈, 栃原しおり, 大池有紀, 胡桃坂真由子, 葉山智工, 宮腰藍衣, 伊集院昌郁, 濱田春, 末吉寿実鼓, 戸田美咲, 土屋尚輝, 湯村寧, 竹島徹平, 黒田晋之介, 宮城悦子, 榊原秀也, 村瀬真理子

    日本生殖医学会雑誌   69 ( 4 )   2024

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  • 精子不動症に対しTESE-ICSIを施行した3症例

    三村 昇, 竹島 徹平, 青木 駿, 齋藤 智樹, 苅部 樹里衣, 黒田 晋之介, 古目谷 暢, 戸田 美咲, 末吉 寿実鼓, 濱田 春, 伊集院 昌郁, 宮腰 藍衣, 葉山 智工, 齋藤 満里奈, 栃原 しおり, 上野 寛枝, 村瀬 真理子, 湯村 寧

    日本生殖医学会雑誌   68 ( 4 )   469 - 469   2023.10

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  • 当院のTESE-ICSIにおけるペントキシフィリン適用の検討

    戸田美咲, 戸田美咲, 戸田美咲, 末吉寿実鼓, 濱田春, 伊集院昌郁, 宮腰藍衣, 葉山智工, 胡桃坂真由子, 大池有紀, 栃原しおり, 齋藤満里奈, 上野寛枝, 竹島徹平, 湯村寧, 榊原秀也, 宮城悦子, 村瀬真理子

    日本生殖医学会雑誌   68 ( 4 )   2023

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  • 初期胚移植胚選別法mBSの有効性評価

    上野寛枝, 齋藤満里奈, 栃原しおり, 大池有紀, 胡桃坂真由子, 伊集院昌郁, 葉山智工, 濱田春, 宮腰藍衣, 末吉寿実鼓, 戸田美咲, 湯村寧, 竹島徹平, 黒田晋之介, 宮城悦子, 榊原秀也, 村瀬真理子

    日本生殖医学会雑誌   68 ( 4 )   2023

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  • 精巣胚細胞腫瘍患者の治療前凍結精子を用いたICSI妊娠では流産率が高い

    濱田春, 末吉寿実鼓, 戸田美咲, 伊集院昌郁, 宮腰藍衣, 葉山智工, 葉山智工, 胡桃坂真由子, 大池有紀, 栃原しおり, 齋藤満里奈, 上野寛枝, 竹島徹平, 湯村寧, 榊原秀也, 宮城悦子, 村瀬真理子

    日本生殖医学会雑誌   68 ( 4 )   2023

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  • 当院における性腺毒性低-中リスク化学療法後の妊娠転帰

    伊集院昌郁, 末吉寿実鼓, 戸田美咲, 濱田春, 葉山智工, 胡桃坂真由子, 大池有紀, 栃原しおり, 齋藤満里奈, 上野寛枝, 竹島徹平, 湯村寧, 宮城悦子, 村瀬真理子

    日本生殖医学会雑誌   68 ( 4 )   2023

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  • 当院独自の形態動態学的分類mBSと胚染色異常との関連性

    栃原しおり, 胡桃坂真由子, 大池有紀, 齋藤満里奈, 上野寛枝, 末吉寿実鼓, 伊集院昌郁, 末吉寿実鼓, 伊集院昌郁, 戸田美咲, 濱田春, 宮腰藍衣, 葉山智工, 葉山智工, 竹島徹平, 湯村寧, 宮城悦子, 宮城悦子, 榊原秀也, 村瀬真理子

    日本生殖医学会雑誌   68 ( 4 )   2023

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  • 無精子症患者に対してBEP4コース実施後にMD-TESEで精子を回収し生児を得た一例

    末吉寿実鼓, 村瀬真理子, 濱田春, 伊集院昌郁, 宮腰藍衣, 葉山智工, 竹島徹平, 湯村寧

    日本生殖医学会雑誌   67 ( 4 )   2022

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  • ターナー症候群の免疫異常と不妊・流産の関係

    宮腰藍衣, 葉山智工, 末吉寿実鼓, 末吉寿実鼓, 伊集院昌郁, 伊集院昌郁, 濱田春, 濱田春, 西真裕子, 齋藤満里奈, 栃原しおり, 上野寛枝, 宮城悦子, 榊原秀也, 村瀬真理子

    日本生殖医学会雑誌   67 ( 4 )   2022

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  • 男性不妊患者における精液中ニトロソ化ストレスの精子に対する影響

    湯村 寧, 竹島 徹平, 黒田 晋之介, 古目谷 暢, 齋藤 智樹, 葉山 智工, 宮腰 藍衣, 濱田 春, 村瀬 真理子, 吉田 薫, 塚本 浩之, 秋葉 陽子, 山本 みずき, 上野 寛枝, 齋藤 満里奈, 西 真裕子, 栃原 しおり

    日本生殖医学会雑誌   66 ( 4 )   395 - 395   2021.10

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  • 精液中炎症マーカーGranulocyte elastase(GE)と酸化ストレス,精子運動パラメーターとの関連

    石橋 裕香里, 齋藤 智樹, 苅部 樹里衣, 古目谷 暢, 黒田 晋之介, 竹島 徹平, 湯村 寧, 濱田 春, 宮腰 藍衣, 葉山 智工, 村瀬 真理子, 栃原 しおり, 西 真裕子, 齋藤 満里奈, 上野 寛枝, 山本 みずき, 吉田 薫, 塚本 浩之, 秋葉 陽子

    日本生殖医学会雑誌   66 ( 4 )   358 - 358   2021.10

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  • 人工知能補助による顕微受精時の良好精子特徴分析と精子Grading法の開発

    山本 みずき, 上野 寛枝, 齋藤 満里奈, 西 真裕子, 竹島 徹平, 齋藤 智樹, 栃原 しおり, 古目谷 暢, 黒田 晋之介, 葉山 智工, 宮腰 藍衣, 濱田 春, 村瀬 真理子, 湯村 寧

    日本生殖医学会雑誌   66 ( 4 )   281 - 281   2021.10

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  • HIGH MITOCHONDRIAL DNA REPLICATION IN EMBRYOS DERIVED FROM MYOTONIC DYSTROPHY 1 FEMALE.

    Akifumi Ijuin, Tomonari Hayama, Mizuki Yamamoto, Hiroe Ueno, Haru Hamada, Ai Miyakoshi, Mayuko Nishi, Marina Saito, Shiori Tochihara, Teppei Takeshima, Shinnosuke Kuroda, Hideya Sakakibara, Yasushi Yumura, Etsuko Miyagi, Mariko Murase

    FERTILITY AND STERILITY   116 ( 3 )   E225 - E225   2021.9

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  • ADD-ON EFFECT OF ORAL ANTIOXIDANT THERAPY TO SURGICAL VARICOCELECTOMY ON THE OUTCOME OF ASSISTED REPRODUCTIVE TECHNOLOGY: A SINGLE-CENTER RETROSPECTIVE COHORT STUDY.

    Teppei Takeshima, Shinnosuke Kuroda, Mitsuru Komeya, Marina Saito, Mayuko Nishi, Hiroe Ueno, Mizuki Yamamoto, Akifumi Ijuin, Haru Hamada, Ai Miyakoshi, Tomonari Hayama, Mariko Murase, Yasushi Yumura

    FERTILITY AND STERILITY   116 ( 3 )   E334 - E334   2021.9

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  • THE EFFICACY OF ONCO-TESTICULAR SPERM EXTRACTION (ONCO-TESE): A SINGLE-CENTER ANALYSIS.

    Shinnosuke Kuroda, Kimitsugu Usui, Teppei Takeshima, Mitsuru Komeya, Tomonari Hayama, Hiroji Uemura, Yasushi Yumura

    FERTILITY AND STERILITY   114 ( 3 )   E255 - E256   2020.9

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  • SURVEY ON PERCEPTION OF GERMLINE GENE THERAPY AMONG JAPANESE MEDICAL STUDENT.

    Tomonari Hayama, Akifumi Ijuin, Ai Miyakoshi, Haru Hamada, Mitsuru Komeya, Teppei Takeshima, Shinnosuke Kuroda, Yasushi Yumura, Mariko Murase, Etsuko Miyagi, Hideya Sakakibara

    FERTILITY AND STERILITY   114 ( 3 )   E198 - E198   2020.9

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  • 院内e learningによる妊孕性温存治療の啓発効果

    湯村 寧, 村瀬 真理子, 葉山 智工, 竹島 徹平, 黒田 晋之介, 宮腰 藍衣, 伊集院 昌郁, 星 るり子, 和田 伸子

    日本がん・生殖医療学会誌   3 ( 1 )   104 - 104   2020.1

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  • Reduced response to ovarian stimulations in women carrying pathogenic mtDNA mutations

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

    MITOCHONDRION   31   97 - 97   2016.11

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  • Interspecies Reproductive Barrier due mtDNA Divergence

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

    MITOCHONDRION   31   99 - 99   2016.11

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  • Somatic mtDNA mutations in wild type and Polg mutator mice

    Yeonmi Lee, Hong Ma, Eunju Kang, Rebecca Tippner-Hedges, Nuria Marti Gutierrez, Tomonari Hayama, Crystal Van Dyken, Ying Li, Riffat Ahmed, Amy Koski, Shoukhrat Mitalipov

    MITOCHONDRION   31   97 - 97   2016.11

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  • Accumulation of Somatic Mitochondrial DNA Mutations in iPSCs from Elderly Humans

    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

    MITOCHONDRION   31   98 - 98   2016.11

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  • Generation of mice with pathogenic mitochondrial DNA mutations

    Tomonari Hayama, Crystal Van Dyken, Ying Li, Nuria Marti Gutierrez, Eunju Kang, Yeonmi Lee, Chunlong Xu, Trevor J. McGill, Michael Andrews, Rebecca Tippner-Hedges, Riffat Ahmed, Amy Koski, Hong Ma, Shoukhrat Mitalipov

    MITOCHONDRION   31   94 - 94   2016.11

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  • 免疫不全動物を用いたラット/マウス異種異所発生による始原生殖細胞からの生殖腺様組織誘導

    葉山 智工, 山口 智之, 加藤 めぐみ, 三宝 誠, 田村 千尋, 海野 あゆみ, 瓦井 麻美, 佐藤 秀征, 小林 俊寛, 平林 真澄, 中内 啓光

    日本生殖医学会雑誌   58 ( 4 )   328 - 328   2013.10

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  • Diagnosis and management of women with DSD (disorder of sex development)

    Tomonari Hayama, Aiko Kawano, Reiko Nakamura, Yuko Tagami, Ryoko Asano, Akiko Nara, Yasuko Suzuki, Tomoko Nagata, Yoshiyuki Nomura, Kazuko Sumitomo, Mariko Murase, Maki Takei, Hideya Sakakibara, Fumiki Hirahara

    ENDOCRINE JOURNAL   57   S598 - S598   2010.3

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  • P3-36 新規骨形成マーカーPINPを用いた骨粗鬆症治療の効果判定(Group102 骨粗鬆症2,一般演題,第62回日本産科婦人科学会学術講演会)

    野村 可之, 善方 裕美, 浅野 涼子, 葉山 智工, 倉澤 健太郎, 小林 有紀, 住友 和子, 菊地 律子, 榊原 秀也, 茶木 修, 平原 史樹

    日本産科婦人科學會雜誌   62 ( 2 )   636 - 636   2010

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  • P3-25 SERM治療の有用性 : 当科における長期治療成績から(Group101 骨粗鬆症1,一般演題,第62回日本産科婦人科学会学術講演会)

    中村 麗子, 善方 裕美, 浅野 涼子, 葉山 智工, 野村 可之, 小林 有紀, 住友 和子, 菊地 律子, 榊原 秀也, 平原 史樹, 倉澤 健太郎, 茶木 修

    日本産科婦人科學會雜誌   62 ( 2 )   632 - 632   2010

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  • P3-35 新しい骨代謝マーカーucOCの臨床における有用性について(Group102 骨粗鬆症2,一般演題,第62回日本産科婦人科学会学術講演会)

    善方 裕美, 浅野 涼子, 葉山 智工, 野村 可之, 倉澤 健太郎, 小林 有紀, 住友 和子, 菊地 律子, 榊原 秀也, 茶木 修, 平原 史樹

    日本産科婦人科學會雜誌   62 ( 2 )   636 - 636   2010

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  • P2-420 胎児頻脈性不整脈に対する胎児治療として,塩酸ソタロールと酢酸フレカイニドを併用した経母体投与が有効であった一例(Group95 胎児・新生児7,一般演題,第62回日本産科婦人科学会学術講演会)

    丸山 康世, 村瀬 真理子, 葉山 智工, 平原 史樹, 長瀬 寛美, 田野島 美城, 斉藤 圭介, 奥田 美加, 高橋 恒男, 石川 浩史

    日本産科婦人科學會雜誌   62 ( 2 )   604 - 604   2010

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  • P2-175 当院で経験した髄膜瘤80例の検討(Group55 胎児新生児7,一般演題,第61回日本産科婦人科学会学術講演会)

    小澤 克典, 葉山 智工, 吉崎 敦雄, 丸山 康世, 長瀬 寛美, 石川 浩史

    日本産科婦人科學會雜誌   61 ( 2 )   584 - 584   2009

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  • P2-181 当院で出産した18トリソミー症例の検討(Group56 胎児新生児8,一般演題,第61回日本産科婦人科学会学術講演会)

    長瀬 寛美, 葉山 智工, 吉崎 敦雄, 丸山 康世, 小澤 克典, 石川 浩史

    日本産科婦人科學會雜誌   61 ( 2 )   586 - 586   2009

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  • P1-157 胎児異常疑いと診断された妊娠週数の年次推移に関する検討(Group21 胎児新生児4,一般演題,第61回日本産科婦人科学会学術講演会)

    石川 浩史, 吉崎 敦雄, 葉山 智工, 小澤 克典, 丸山 康世, 長瀬 寛美

    日本産科婦人科學會雜誌   61 ( 2 )   498 - 498   2009

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  • P2-168 胎児超音波検査で四肢短縮を指摘された症例の検討(Group54 胎児新生児6,一般演題,第61回日本産科婦人科学会学術講演会)

    吉崎 敦雄, 葉山 智工, 丸山 康世, 小澤 克典, 長瀬 寛美, 石川 浩史

    日本産科婦人科學會雜誌   61 ( 2 )   581 - 581   2009

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  • P2-466 ターナー女性の健康管理における小児科から産婦人科への紹介転機のあり方に関する検討(Group 175 思春期・更年期・老年期I,一般演題,講演要旨,第58回日本産科婦人科学会学術講演会)

    武居 麻紀, 榊原 秀也, 吉田 浩, 神田 義明, 武井 美城, 大前 真理, 葉山 智工, 石川 雅彦, 平原 史樹

    日本産科婦人科學會雜誌   58 ( 2 )   747 - 747   2006

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  • P2-465 当科女性健康外来におけるターナー女性の卵巣機能に関する検討(Group 175 思春期・更年期・老年期I,一般演題,講演要旨,第58回日本産科婦人科学会学術講演会)

    勝畑 有紀子, 榊原 秀也, 武居 麻紀, 吉田 浩, 神田 義明, 武井 美城, 大前 真理, 葉山 智工, 石川 雅彦, 平原 史樹

    日本産科婦人科學會雜誌   58 ( 2 )   746 - 746   2006

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  • 甲状腺クリーゼを合併した広汎性発達障害の1例

    須田 顕, 長谷川 花, 山田 康弘, 鈴木 東洋, 葉山 智工, 小田原 俊成

    神奈川県精神医学会誌   ( 55 )   83 - 83   2005.12

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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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