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Elucidation of new molecular mechanisms involved in postnatal testicular development and functional acquisition

Research Project

Project/Area Number 19K09682
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56030:Urology-related
Research InstitutionNational Center for Child Health and Development

Principal Investigator

Miyado Mami  国立研究開発法人国立成育医療研究センター, 分子内分泌研究部, 上級研究員 (00386252)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords精巣 / 生殖機能 / モデル動物 / Y染色体喪失 / 性分化疾患 / 子宮内低栄養 / MAMLD1 / 培養細胞
Outline of Research at the Start

本研究では、性分化関連因子であるMAMLD1が生後の精巣の発育および機能獲得にどのように関与しているかを明らかにし、生後の精巣においてMAMLD1を介する新たな分子機構を解明する。モデル動物の表現型解析と培養細胞をもちいて機能解析を行い、MAMLD1が男性ホルモン産生・代謝に与える影響を明らかにする。本研究により得られる知見は、雄性生殖機能獲得の理解につながり、性分化疾患および生殖機能障害の発症機序の解明に貢献すると考えられる。

Outline of Final Research Achievements

To identify missing pieces hidden in already known mechanisms of postnatal testicular development and functional acquisition, we performed this study using a set of disease model animals and samples obtained from patients. Subsequently, we obtained remarkable results as followings: (1) Extra-mitochondrial CS (eCS) suppresses age-dependent male infertility; (2) The frequency of leukocyte mLOY in reproductive-aged men with spermatogenic failure is rare; (3) Major histocompatibility complex class I expressed in sperm blocks polyspermy; and (4) Intrauterine hyponutrition reduces fetal testosterone production and postnatal sperm count in the mouse.

Academic Significance and Societal Importance of the Research Achievements

本研究では、遺伝子機能の変化やY染色体のコピー変化が精巣機能や精子形成に与える影響を明らかにした。モデル動物と疾患患者の解析を行い、精巣・精子形成および男性ホルモン産生に関わる新たな分子機構を見出した。本研究の成果は、性分化疾患や男性不妊症などの生殖機能障害発症機序の解明に結び付くことが期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (33 results)

All 2022 2021 2020 2019

All Journal Article (25 results) (of which Peer Reviewed: 22 results,  Open Access: 20 results) Presentation (8 results) (of which Invited: 3 results)

  • [Journal Article] Intrauterine hyponutrition reduces fetal testosterone production and postnatal sperm count in the mouse.2022

    • Author(s)
      Fujisawa Y, Ono H, Konno A, Yao I, Itoh H, Baba T, Morohashi K, Katoh-Fukui Y, Miyado M, Fukami M and Ogata T.
    • Journal Title

      Journal of the Endocrine Society

      Volume: 6 Issue: 4 Pages: 1-11

    • DOI

      10.1210/jendso/bvac022

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suppressive role of lactoferrin in overweight-related female fertility problems.2022

    • Author(s)
      Sato B, Kanai S, Sakaguchi D, Yajima K, Matsumoto Y, Morohoshi K, Kagaya S, Izumo N, Ichinose M, Kang W, Miyado M, Miyado K and Kawano N.
    • Journal Title

      Nutrients

      Volume: 14 Issue: 5 Pages: 938-938

    • DOI

      10.3390/nu14050938

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mosaic loss of the Y chromosome and men's health.2022

    • Author(s)
      Fukami M and Miyado M.
    • Journal Title

      Reproductive Medicine and Biology

      Volume: 21 Issue: 1

    • DOI

      10.1002/rmb2.12445

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MAMLD1 and differences/disorders of sex development: An update.2022

    • Author(s)
      Miyado M, Fukami M and Ogata T.
    • Journal Title

      Sexual Development

      Volume: 印刷中 Issue: 2-3 Pages: 1-12

    • DOI

      10.1159/000519298

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structural and numerical Y chromosomal variations in elderly men identified through multiplex ligation-dependent probe amplification.2021

    • Author(s)
      Ogiwara Y, Miyado M, Suzuki E, Niida S, Ozaki K and Fukami M.
    • Journal Title

      Journal of Human Genetics

      Volume: 66 Issue: 12 Pages: 1181-1184

    • DOI

      10.1038/s10038-021-00943-9

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantification of androgens and their precursors in full-term human placenta.2021

    • Author(s)
      Yoshida T, Matsumoto K, Miyado M, Miyashiro Y, Sago H, Horikawa R and Fukami M.
    • Journal Title

      European Journal of Endocrinology

      Volume: 185 Issue: 5 Pages: K7-K11

    • DOI

      10.1530/eje-21-0312

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of liquid-liquid separation in endocrine and living cells.2021

    • Author(s)
      Akiba K, Katoh-Fukui Y, Yoshida K, Narumi S, Miyado M, Hasegawa Y and Fukami M.
    • Journal Title

      Journal of the Endocrine Society

      Volume: 5 Issue: 10

    • DOI

      10.1210/jendso/bvab126

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] GNAS-Gsα機能亢進型バリアントに起因する新たな先天性腎疾患の発見.2021

    • Author(s)
      宮戸真美,緒方勤,深見真紀.
    • Journal Title

      糖尿病・内分泌代謝科(科学評論社)

      Volume: 53 Pages: 71-77

    • NAID

      40022653122

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Similar responsiveness between C57BL/6N and C57BL/6J mouse substrains to superovulation.2021

    • Author(s)
      Shindo M, Tsumura H, Miyado K, Kang W, Kawano N, Yoshida T, Fukami M and Miyado M.
    • Journal Title

      microPublication Biology

      Volume: 0 Pages: 000375-000375

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circulating steroids and mood disorders in patients with polycystic ovary syndrome.2021

    • Author(s)
      Yoshida T, Saito K, Kawamura T, Ishikawa T, Kato T, Matsubara K, Miyasaka N, Miyado M and Fukami M.
    • Journal Title

      Steroids

      Volume: 165 Pages: 108748-108748

    • DOI

      10.1016/j.steroids.2020.108748

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuronal expression of Ca2+ oscillation initiator is linked to rapid neonatal growth in mice.2020

    • Author(s)
      Kang W, Yamatoya K, Miyado K, Miyado M and Miyamoto Y.
    • Journal Title

      microPublication Biology

      Volume: 0 Pages: 000325-000325

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suppression of Non-Random Fertilization by MHC Class I Antigens2020

    • Author(s)
      Kamiya Junki、Kang Woojin、Yoshida Keiichi、Takagi Ryota、Kanai Seiya、Hanai Maito、Nakamura Akihiro、Yamada Mitsutoshi、Miyamoto Yoshitaka、Miyado Mami、Kuroki Yoko、Hayashi Yoshiki、Umezawa Akihiro、Kawano Natsuko、Miyado Kenji
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 22 Pages: 8731-8731

    • DOI

      10.3390/ijms21228731

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nonsense-associated altered splicing of MAP3K1 in two siblings with 46,XY disorders of sex development.2020

    • Author(s)
      Igarashi M, Masunaga Y, Hasegawa Y, Kinjo K, Miyado M, Saitsu H, Kato-Fukui Y, Horikawa R, Okubo Y, Ogata T and Fukami M.
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 17375-17375

    • DOI

      10.1038/s41598-020-74405-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rare variant of the epigenetic regulator SMCHD1 in a patient with pituitary hormone deficiency.2020

    • Author(s)
      Kinjo K, Nagasaki K, Muroya K, Suzuki E, Ishiwata K, Nakabayashi K, Hattori A, Nagao K, Nozawa R-S, Obuse C, Miyado K, Ogata T, Fukami M and Miyado M.
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 10985-10985

    • DOI

      10.1038/s41598-020-67715-x

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 性スペクトラム.2020

    • Author(s)
      宮戸真美,福井由宇子,深見真紀.
    • Journal Title

      泌尿器科(科学評論社)

      Volume: 12 Pages: 184-190

    • NAID

      40022337212

    • Related Report
      2020 Research-status Report
  • [Journal Article] Copy-number analysis of Y-linked loci in young men with non-obstructive azoospermia: Implications for the rarity of early onset mosaic loss of chromosome Y.2020

    • Author(s)
      Suzuki E, Kobori Y, Katsumi M, Ushijima K, Uchiyama T, Okada H, Miyado M and Fukami M.
    • Journal Title

      Reprod Med Biol.

      Volume: 19 Issue: 2 Pages: 178-181

    • DOI

      10.1002/rmb2.12321

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Random X chromosome inactivation in patients with Klinefelter syndrome.2020

    • Author(s)
      Kinjo K, Yoshida T, Kobori Y, Okada H, Suzuki E, Ogata T, Miyado M and Fukami M.
    • Journal Title

      Mol Cell Pediatr.

      Volume: 7 Issue: 1 Pages: 1-1

    • DOI

      10.1186/s40348-020-0093-x

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extra-mitochondrial citrate synthase initiates calcium oscillation and suppresses age-dependent sperm dysfunction.2020

    • Author(s)
      Kang W, Harada Y, Yamatoya K, Kawano N, Kanai S, Miyamoto Y, Nakamura A, Miyado M, Hayashi Y, Kuroki Y, Saito H, Iwao Y, Umezawa A and Miyado K.
    • Journal Title

      Lab Invest.

      Volume: 100 Issue: 4 Pages: 665-665

    • DOI

      10.1038/s41374-019-0369-8

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reply: Artificial cycle ‘per se’ or the specific protocol of endometrial preparation as responsible for obstetric complications of frozen cycle?2019

    • Author(s)
      Saito K, Kuwahara A, Ishikawa T, Morisaki N, Miyado M, Miyado K, Fukami M, Miyasaka N, Ishihara O, Irahara M and Saito H.
    • Journal Title

      Human Reproduction

      Volume: 34 Issue: 12 Pages: 2554-2555

    • DOI

      10.1093/humrep/dez221

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Aneuploid rescue precedes X-chromosome inactivation and increases the incidence of its skewness by reducing the size of the embryonic progenitor cell pool.2019

    • Author(s)
      Yoshida T, Miyado M, Mikami M, Suzuki E, Kinjo K, Matsubara K, Ogata T, Akutsu H, Kagami M and Fukami M.
    • Journal Title

      Human Reproduction

      Volume: 34 Issue: 9 Pages: 1762-1769

    • DOI

      10.1093/humrep/dez117

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endometrial preparation methods for frozen-thawed embryo transfer are associated with altered risks of hypertensive disorders of pregnancy, placenta accreta, and gestational diabetes mellitus.2019

    • Author(s)
      Saito K, Kuwahara A, Ishikawa T, Morisaki N, Miyado M, Miyado K, Fukami M, Miyasaka N, Ishihara O, Irahara M and Saito H.
    • Journal Title

      Human Reproduction

      Volume: 34 Issue: 8 Pages: 1567-1575

    • DOI

      10.1093/humrep/dez079

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Calaxin is required for cilia-driven determination of vertebrate laterality2019

    • Author(s)
      Sasaki Keita、Shiba Kogiku、Nakamura Akihiro、Kawano Natsuko、Satouh Yuhkoh、Yamaguchi Hiroshi、Morikawa Motohiro、Shibata Daisuke、Yanase Ryuji、Jokura Kei、Nomura Mami、Miyado Mami、Takada Shuji、Ueno Hironori、Nonaka Shigenori、Baba Tadashi、Ikawa Masahito、Kikkawa Masahide、Miyado Kenji、Inaba Kazuo
    • Journal Title

      Communications Biology

      Volume: 2 Issue: 1 Pages: 226-226

    • DOI

      10.1038/s42003-019-0462-y

    • NAID

      120006957456

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA Methylation Status of SHOX-Flanking CpG Islands in Healthy Individuals and Short Stature Patients with Pseudoautosomal Copy Number Variations.2019

    • Author(s)
      Ogushi K, Muroya K, Shima H, Jinno T, Miyado M and Fukami M.
    • Journal Title

      Cytogenetic and Genome Research

      Volume: 158 Issue: 2 Pages: 56-62

    • DOI

      10.1159/000500468

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Microexosomes versus exosomes: Shared components but distinct structures2019

    • Author(s)
      Miyado Mami、Kang Woojin、Kawano Natsuko、Miyado Kenji
    • Journal Title

      Regenerative Therapy

      Volume: 11 Pages: 31-33

    • DOI

      10.1016/j.reth.2019.04.013

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Y染色体喪失とヒトの性スペクトラム.2019

    • Author(s)
      宮戸真美,深見真紀.
    • Journal Title

      実験医学

      Volume: 37 Pages: 1434-1438

    • Related Report
      2019 Research-status Report
  • [Presentation] Y染色体喪失が生じる時期と関連疾患の解明.2021

    • Author(s)
      宮戸真美,室谷浩二,深見真紀.
    • Organizer
      第39回日本アンドロロジー学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] ヒトY染色体喪失に関連する疾患の解明.2020

    • Author(s)
      宮戸真美,深見真紀.
    • Organizer
      内分泌・代謝学共同利用共同研究拠点 若手研究発表会
    • Related Report
      2019 Research-status Report
  • [Presentation] 世界初の生殖細胞由来GNAS機能亢進型バリアントの同定.2020

    • Author(s)
      宮戸真美,深見真紀,緒方 勤.
    • Organizer
      第30回バゾプレシン研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] ヒトの性スペクトラム:Y染色体喪失をモデルとして.2019

    • Author(s)
      宮戸真美,深見真紀.
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Germline-derived gain-of-function variants of Gsα-coding GNAS gene identified in nephrogenic syndrome of inappropriate antidiuresis: the first report.2019

    • Author(s)
      Miyado M, Fukami M, Matsubara Y, Tanaka Y, Sasaki G, Nagasaki K, Masunaga Y, Saitsu H and Ogata T.
    • Organizer
      第53回日本小児内分泌学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 日本で実験動物化された非げっ歯類スンクスの特徴と有用性.2019

    • Author(s)
      宮戸真美,宮戸健二.
    • Organizer
      第90回日本動物学会大阪大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] ヒトで同定された変異導入マウスの解析.2019

    • Author(s)
      宮戸真美.
    • Organizer
      新しいゲノム編集技術によるヒト疾患モデルマウスの効率的作製(キックオフミーティング)
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 非閉塞性無精子症の新たな原因遺伝子の同定.2019

    • Author(s)
      宮戸真美,中村 繁,小堀善友,田中葉子,石川博通,吉田 淳,上田善彦,岡田 弘,緒方 勤,深見真紀.
    • Organizer
      第38回日本アンドロロジー学会学術大会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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