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Investigation of a regulatory mechanism underlying androgen production in the fetal testis

Research Project

Project/Area Number 24790303
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General medical chemistry
Research InstitutionNational Research Institute for Child Health and Development

Principal Investigator

MIYADO Mami  独立行政法人国立成育医療研究センター, 分子内分泌研究部, 研究員 (00386252)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords男性ホルモン産生 / MAMLD1 / Mamld1
Research Abstract

MAMLD1 (Mastermind-like domain containing 1) has been identified as a gene responsible for with hypospadias in humans. The Mamld1 mRNA expression was gradually and steadily increased from 12.5 to 18.5 day post coitum in the fetal testis of wild-type male mice. To study the role of MAMLD1 in mice, we produced Mamld1 knockout mice. Mamld1 knockout male mice showed mildly but significantly reduced fetal testicular mRNA levels of genes exclusively expressed in Leydig cells (Star, Cyp11a1, Cyp17a1, and Hsd3b1). These results provide the evidence that MAMLD1 plays a role in androgen production, indicating the presence of a mechanism shared between mouse and human. Further studies will explore the MAMLD1-dependent molecular network in the steroid hormone production and the pathological condition of MAMLD1-mutated patients.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (21 results)

All 2014 2013 2012

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 1 results) Presentation (12 results)

  • [Journal Article] Aromatase excess syndrome : a rare autosomal dominant disorder leading to pre or peri - pubertal onset gynecomastia2014

    • Author(s)
      Fukami M, Miyado M, Nagasaki K, Shozu M, and Ogata T
    • Journal Title

      Pediatr Endocrinol Rev

      Volume: 11 (3) Pages: 298-305

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aromatase Excess Syndrome: A Rare Autosomal Dominant Disorder Leading to Pre- or Peri-pubertal Onset Gynecomastia.2014

    • Author(s)
      Fukami M, Miyado M, Nakabayashi K, Shozu M, Ogata T.
    • Journal Title

      Pediatr Endocrinol Rev.

      Volume: 11 Pages: 298-305

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] De novo frameshift mutation in fibroblast growth factor 8 in a male patient with gonadotropin deficiency2013

    • Author(s)
      Suzuki E, Yatsuga S, Igarashi M, Miyado M, Nakabayashi K, Hayashi K, Hata K, Umezawa A, Yamada G, Ogata T, Fukami M*
    • Journal Title

      Horm Res Paediatr ,

      Volume: 81 Issue: 2 Pages: 139-144

    • DOI

      10.1159/000355380

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aromatase excess syndrome in a family with upstream deletion of CYP19A12013

    • Author(s)
      Shihara D, Miyado M, Nakabayashi K, Shozu M, Nagasaki K, Ogata T, Fukami M*
    • Journal Title

      Clin Endocrinol,

      Volume: Epub ahead of print Issue: 2 Pages: 314-316

    • DOI

      10.1111/cen.12329

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Individual variation of the genetic response to bisphenol a in human foreskin fibroblast cells derived from cryptorchidism and hypospadias patients2012

    • Author(s)
      Qin XY, Sone H, Kojima Y, Mizuno K, Ueoka K, Muroya K, Miyado M, Hisada A, Zaha H, Fukuda T, Yoshinaga J, Yonemoto J, Kohri K, Hayashi Y, Fukami M, Ogata T
    • Journal Title

      PLoS One

      Volume: 7 Issue: 12 Pages: e52756-e52756

    • DOI

      10.1371/journal.pone.0052756

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] CD81 and CD9 work independently as extracellular components upon fusion of sperm and oocyt2012

    • Author(s)
      Ohnami N, Nakamura A, Miyado M, Sato M, Kawano N, Yoshida K, Harada Y, Takezawa Y, Kanai S, Ono C, Takahashi Y, Kimura K, Shida T, Miyado K, Umezawa A
    • Journal Title

      Biol Open

      Volume: 1(7) Issue: 7 Pages: 640-647

    • DOI

      10.1242/bio.20121420

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mamld1 deficiency significantly reduces mRNA expression levels of multiple genes expressed in mouse fetal Leydig cells but permits normal genital and reproductive development2012

    • Author(s)
      Miyado M, Nakamura M, Miyado K, Morohashi K, Sano S, Nagata E, Fukami M, Ogata T
    • Journal Title

      Endocrinology

      Volume: 153(12) Issue: 12 Pages: 6033-6040

    • DOI

      10.1210/en.2012-1324

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Paternal uniparental disomy 14 and related disorders: placental gene expression analyses and histological examinations.2012

    • Author(s)
      M. Kagam, K. Matsuoka, T. Nagai, M. Yamanaka, K. Kurosawa, N. Suzumori, Y. Sekita, M. Miyado, K. Matsubara, T. Fuke, F. Kato, M. Fukami, T. Ogata.
    • Journal Title

      Epigenetics

      Volume: 7 Issue: 10 Pages: 1142-1150

    • DOI

      10.4161/epi.21937

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of novel low-dose bisphenol A targets in human foreskin fibroblast cells derived from hypospadias patients.2012

    • Author(s)
      X.Y. Qin, M. Miyado, Y. Kojima, H. Zaha, H. Akanuma, Q. Zeng, J. Yoshinaga, J. Yonemoto, M. Fukami, T. Ogata, H. Sone.
    • Journal Title

      PLoS One

      Volume: 7 Issue: 5 Pages: e36711-e36711

    • DOI

      10.1371/journal.pone.0036711

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Mamld1遺伝子欠損妊娠マウスは黄体退縮不全による分娩遅延を呈する2013

    • Author(s)
      (1)宮戸真美、志原大蔵、宮戸健二、緒方勤、深見真紀
    • Organizer
      第18回日本生殖内分泌学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2013-12-07
    • Related Report
      2013 Final Research Report
  • [Presentation] Mamld1遺伝子欠損は、成獣マウスの精巣サイズ減少を招くが、妊孕性には影響を与えない2013

    • Author(s)
      (2)宮戸真美、志原大蔵、宮戸健二、緒方勤、深見真紀
    • Organizer
      第36回日本分子生物学会
    • Place of Presentation
      神戸
    • Year and Date
      2013-12-05
    • Related Report
      2013 Final Research Report
  • [Presentation] Mamld1遺伝子欠損は、妊娠マウスにおける黄体退縮不全と分娩遅延を招く2013

    • Author(s)
      (3)宮戸真美、志原大蔵、宮戸健二、緒方勤、深見真紀
    • Organizer
      第21回日本ステロイドホルモン学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2013-11-16
    • Related Report
      2013 Final Research Report
  • [Presentation] Mamld1はマウス分娩開始シグナルに関与する卵巣ステロイド産生調節因子である2013

    • Author(s)
      (4)宮戸真美、志原大蔵、宮戸健二、緒方勤、深見真紀
    • Organizer
      第47回日本小児内分泌学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2013-10-12
    • Related Report
      2013 Final Research Report
  • [Presentation] Mamld1遺伝子欠損妊娠マウスは黄体退縮不全による分娩遅延を呈する.2013

    • Author(s)
      宮戸真美,志原大蔵,宮戸健二,緒方 勤,深見真紀.
    • Organizer
      第18回日本生殖内分泌学会学術集会
    • Place of Presentation
      シェーンバッハ・サボー(砂防会館別館,東京)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Mamld1遺伝子欠損は,成獣マウスの精巣サイズ減少を招くが,妊孕性には影響を与えない.2013

    • Author(s)
      宮戸真美,志原大蔵,宮戸健二,緒方 勤,深見真紀.
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(兵庫)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Mamld1遺伝子欠損は,妊娠マウスにおける黄体退縮不全と分娩遅延を招く.2013

    • Author(s)
      宮戸真美,志原大蔵,宮戸健二,緒方 勤,深見真紀.
    • Organizer
      第21回日本ステロイドホルモン学会学術集会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Mamld1はマウス分娩開始シグナルに関与する卵巣ステロイド産生調節因子である.2013

    • Author(s)
      宮戸真美,志原大蔵,宮戸健二,緒方 勤,深見真紀.
    • Organizer
      第47回日本小児内分泌学会学術集会
    • Place of Presentation
      浅草ビューホテル(東京)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 精巣における男性ホルモン産生制御機構 : MAMLD1変異陽性患者とノックアウトマウスからの知見2012

    • Author(s)
      (5)宮戸真美、緒方勤、深見真
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-13
    • Related Report
      2013 Final Research Report
  • [Presentation] 雌性生殖器官におけるMamld1の役割2012

    • Author(s)
      (6)宮戸真美、宮戸健二、緒方勤、深見真紀
    • Organizer
      第46回日本小児内分泌学会
    • Place of Presentation
      大阪
    • Year and Date
      2012-09-29
    • Related Report
      2013 Final Research Report
  • [Presentation] 精巣における男性ホルモン産生制御機構:MAMLD1変異陽性患者とノックアウトマウスからの知見.2012

    • Author(s)
      宮戸真美,緒方勤,深見真紀.
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] 雌性生殖器官におけるMamld1の役割.2012

    • Author(s)
      宮戸真美,宮戸健二,緒方勤,深見真紀.
    • Organizer
      第46回日本小児内分泌学会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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