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

• Project/Area Number: 24790303
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: National 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: ¥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.

Research Products

• [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, Nagasaki K, Shozu M, and Ogata T
  • Journal Title: Pediatr Endocrinol Rev Volume: 11 (3) Pages: 298-305
  • 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
  • Peer Reviewed
• [Journal Article] De novo frameshift mutation in fibroblast growth factor 8 in a male patient with gonadotropin deficiency (2013)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Aromatase excess syndrome in a family with upstream deletion of CYP19A1 (2013)
  • 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
  • Peer Reviewed
• [Journal Article] Individual variation of the genetic response to bisphenol a in human foreskin fibroblast cells derived from cryptorchidism and hypospadias patients (2012)
  • 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
  • Peer Reviewed
• [Journal Article] CD81 and CD9 work independently as extracellular components upon fusion of sperm and oocyt (2012)
  • 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
  • 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 development (2012)
  • 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
  • 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
  • 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
  • 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
• [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
• [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
• [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
• [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）
• [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）
• [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）
• [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）
• [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
• [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
• [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
• [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