The physiological role of CD9 and exosomes in oviducts and uteri

2013 Fiscal Year Final Research Report

• Project/Area Number: 23659788
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: National Research Institute for Child Health and Development
• Principal Investigator: MIYADO KENJI 独立行政法人国立成育医療研究センター, 生殖・細胞医療研究部, 室長 (60324844)
• Project Period (FY): 2011 – 2013
• Keywords: 不妊 / 出産 / 子宮内膜上皮 / 再生 / CD9 / VEGF-A / エキソソーム

Research Abstract

In mammals, the female reproductive tract is remodeled cyclically throughout adult life. Despite the expression of CD9 in the epithelium of the uterus, its role is unclear. Here, we addressed this issue by examining fertilization-competent Cd9-/- mice expressing CD9-GFP in their eggs (Cd9-/-TG). Immunobiochemical analysis demonstrated that CD9 was present in the uterine secretions. Electron microscopic analysis revealed the extracellular matrix-like feature of CD9-containing structures. We also found that the litter size of Cd9-/-TG female mice was significantly reduced after their first birth. Histological analysis revealed severely delayed re-epithelialization of the endometrium both in vitro and in vivo in mice. The quantity of vascular endothelial growth factor-A (VEGF-A) was remarkably reduced in Cd9-/-TG female mice. These results provide the first evidence that CD9-mediated VEGF secretion plays a role in re-epithelialization of the uterus.

Research Products

• [Journal Article] Absence of CD9 reduces endometrial VEGF secretion and impairs uterine repair after parturition (2014)
  • Author(s): Kawano N, Miyado K, Yoshii N, Kanai S, Saito H, Miyado M, Inagaki N, Odawara Y, Hamatani T, Umezawa A
  • Journal Title: Sci Rep Volume: 16;4 Pages: 4701
  • DOI: 10.1038/srep04701.
• [Journal Article] Derivation of human decidua-like cells from amnion and menstrual blood (2014)
  • Author(s): Sugawara K, Hamatani T, Yamada M, Ogawa S, Kamijo S, Kuji N, Akutsu H, Miyado K, Yoshimura Y, Umezawa A
  • Journal Title: Sci Rep Volume: 8;4 Pages: 4599
  • DOI: 10.1038/srep04599.
• [Journal Article] Seminal vesicle protein SVS2 is required for sperm survival in the uterus (2014)
  • Author(s): Kawano N, Araki N, Yoshida K, Hibino T, Ohnami N, Makino M, Kanai S, Hasuwa H, Yoshida M, Miyado K, Umezawa A
  • Journal Title: Proc Natl Acad Sci USA Volume: 18;111(11) Pages: 4145-50
  • DOI: 10.1073/pnas.1320715111.
• [Journal Article] Age-associated telomere shortening in mouse oocytes (2013)
  • Author(s): Yamada-Fukunaga T, Yamada M, Hamatani T, Chikazawa N, Ogawa S, Akutsu H, Miura T, Miyado K, Tarín JJ, Kuji N, Umezawa A, Yoshimura Y
  • Journal Title: Reprod Biol Endocrinol Volume: 21;11 Pages: 108
  • DOI: 10.1186/1477-7827-11-108.
• [Journal Article] β-catenin functions pleiotropically in differentiation and tumorigenesis in mouse embryo-derived stem cells (2013)
  • Author(s): Okumura N, Akutsu H, Sugawara T, Miura T, Takezawa Y, Hosoda A, Yoshida K, Ichida JK, Yamada M, Hamatani T, Kuji N, Miyado K, Yoshimura Y, Umezawa A
  • Journal Title: PLoS One Volume: 14;8(5) Pages: e63265
  • DOI: 10.1371/journal.pone.0063265.
• [Journal Article] Integration of the mouse sperm fertilization-related protein equatorin into the acrosome during spermatogenesis as revealed by super-resolution and immunoelectron microscopy (2013)
  • Author(s): Ito C, Yamatoya K, Yoshida K, Fujimura L, Hatano M, Miyado K, Toshimori K
  • Journal Title: Cell Tissue Res Volume: 352(3) Pages: 739-50
  • DOI: 10.1007/s00441-013-1605-y.
• [Journal Article] テトラスパニンによる受精の膜融合制御 (2013)
  • Author(s): 宮戸健二
  • Journal Title: 医学のあゆみ Volume: Vol.244, No.2 Pages: 181
• [Journal Article] CD81 and CD9 work independently as extracellular components upon fusion of sperm and oocyte (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: 15;1(7) Pages: 640-7
  • DOI: 10.1242/bio.20121420.
• [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) Pages: 6033-40
  • DOI: 10.1210/en.2012-1324.
• [Journal Article] Impaired fertilizing ability of superoxide dismutase 1-deficient mouse sperm during in vitro fertilization (2012)
  • Author(s): Tsunoda S, Kawano N, Miyado K, Kimura N, Fujii J
  • Journal Title: Biol Reprod Volume: 29;87(5) Pages: 121
  • DOI: 10.1095/biolreprod.112.102129.
• [Journal Article] 卵由来エキソソームによる細胞融合の促進機構 (2012)
  • Author(s): 宮戸健二
  • Journal Title: 医学のあゆみ Volume: Vol.241,No.11 Pages: 861-862
• [Journal Article] β-catenin is a molecular switch that regulates transition of cell-cell adhesion to fusion (2011)
  • Author(s): Takezawa Y, Yoshida K, Miyado K, Sato M, Nakamura A, Kawano N, Sakakibara K, Kondo T, Harada Y, Ohnami N, Kanai S, Miyado M, Saito H, Takahashi Y, Akutsu H, Umezawa A
  • Journal Title: Sci Rep Volume: 1 Pages: 68
  • DOI: 10.1038/srep00068.
• [Journal Article] GSTT1 is upregulated by oxidative stress through p38-MK2 signaling pathway in human granulosa cells : possible association with mitochondrial activity (2011)
  • Author(s): Ito M, Imai M, Muraki M, Miyado K, Qin J, Kyuwa S, Yoshikawa Y, Hosoi Y, Saito H, Takahashi Y
  • Journal Title: Aging (Albany NY) Volume: 3(12) Pages: 1213-23
• [Journal Article] Lipid rafts : keys to sperm maturation, fertilization, and early embryogenesis (2011)
  • Author(s): Kawano N, Yoshida K, Miyado K, Yoshida M
  • Journal Title: J Lipids Volume: 2011 Pages: 264706
  • DOI: 10.1155/2011/264706.
• [Journal Article] Lipid rafts enriched in monosialylGb5Cer carrying the stage-specific embryonic antigen-4 epitope are involved in development of mouse preimplantation embryos at cleavage stage (2011)
  • Author(s): Sato B, Katagiri YU, Miyado K, Okino N, Ito M, Akutsu H, Okita H, Umezawa A, Fujimoto J, Toshimori K, Kiyokawa N
  • Journal Title: BMC Dev Biol Volume: 14;11 Pages: 22
  • DOI: 10.1186/1471-213X-11-22.
• [Presentation] テトラスパニンを介した細胞融合の分子メカニズム、ワークショップ「4回膜貫通蛋白質の構造と機能解析の進展」 (2013)
  • Author(s): 宮戸健二
  • Organizer: 第36回日本分子生物学会年会
  • Year and Date: 20130000
• [Presentation] 受精の膜融合におけるCD9およびエキソソームの役割、シンポジウム「バイオイメージングにより明らかにされた動・植物の有性生殖メカニズム」 (2012)
  • Author(s): 宮戸健二
  • Organizer: 日本顕微鏡学会第68回学術講演会
  • Year and Date: 20120000
• [Book] Role of CD9 in sperm-egg fusion and virus-induced cell fusion in mammals. Sexual Reproduction in Animals and Plants, edited by Sawada H, Inoue N, Iwano M (2014)
  • Author(s): Yoshida K, Kawano N, Harada Y, Miyado K
  • Publisher: Springer
• [Book] 動植物の受精学 - 共通性と多様性 - (2014)
  • Author(s): 澤田均, 編
  • Publisher: 化学同人
• [Book] Role of CD9 in sperm-egg fusion and its general role in fusion phenomena. Cell Fusions, edited by Lars-Inge Larsson (2011)
  • Author(s): Kawano N, Harada Y, Yoshida K, Miyado K
  • Publisher: Springer
• [Remarks]
  • URL: http://www.ncchd.go.jp/research/nch/reproduction/staff_miyado.html