Roles of exosomes in reproductive system

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H05475
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Keio University
• Principal Investigator: HAMATANI TOSHIO 慶應義塾大学, 医学部(信濃町), 講師 (60265882)
• Co-Investigator(Kenkyū-buntansha): 宮戸 健二 国立研究開発法人国立成育医療研究センター, 細胞医療研究部, 室長 (60324844) ; 阿久津 英憲 国立研究開発法人国立成育医療研究センター, 生殖医療研究部, 部長 (50347225) ; 山田 満稔 慶應義塾大学, 医学部(信濃町), 助教 (40383864)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: CD9 / 子宮内膜 / 胚 / 細胞外分泌顆粒 / エクソソーム / miRNA

Outline of Final Research Achievements

Tetraspanin membrane protein CD9 was localized predominantly on the basal region of uterine epithelial cells at estrus-stage mice, but relocated to the apical region upon embryo implantation. Extracellular CD9 was most detected in uterine cavity at the estrus stage. In uterine epithelial cells lacking Cd9 genes, membrane projections were shortened and the number of mitochondria was reduced. CD9 repositioning and release may affect both membrane structures and mitochondrial state in the uterus, and contribute to female fertility.
miRNAs secreted via exosome from human blastocysts were profiled using RNA-seq and qRT-PCR. The spent medium in which a good-qualty blastocyst was harvested was analyzed. Some of miRNAs were significantly highly expressed in the spent media derived from blastocysts which resulted in implantation failure, compared to those in pregnancy. The embryo selection based on the detection of the specific miRNAs in spent medium may improve the pregnancy rate.

Free Research Field

生殖医療

Academic Significance and Societal Importance of the Research Achievements

生殖医療における細胞外分泌顆粒（EMV）に関する報告は、我々の論文も含め未だ数報しかない。テトラスパニンCD9はEMVの表面に存在しEMVマーカーとなるため、本研究ではCD9に注目して子宮内膜上皮細胞からのEMV分泌機構を研究する一方、EMVを介して胚から分泌されるmiRNAにも網羅的検討を加えた。EMVの観点から内膜側と胚側の両側の着床因子を検討し、着床の分子機構におけるEMVの寄与が示唆された。これらの結果は、反復着床不全を克服するための胚の質的評価（移植胚の選択）法やEMV（e.g. 自己多血小板血漿）の子宮内投与による着床促進療法などへの臨床応用に繋がることが期待される。