Development of minimally invasive primordial follicle activation method by Hippo signal inhibitor by drug

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K20217
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: International University of Health and Welfare (2018); St. Marianna University School of Medicine (2016-2017)
• Principal Investigator: Sato Yorino 国際医療福祉大学, 医学部, 助教 (00511073)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 卵胞発育 / IVA / Hippoシグナル

Outline of Final Research Achievements

The nuclear translocation of YAP, which is usually an effector protein, is suppressed by Hippo signal. When Hippo signal is suppressed by actin polymerization, follicular development is promoted by YAP translocating into the nucleus and promoting the production of CCN growth factor and the like. We demonstrated that Hippo signal suppression of lysophosphatidic acid (LPA) and thrombin has been reported to promote nuclear translocation of YAP and whether or not the follicular growth promoting effect is present. We confirmed that the expression of CCN growth factor, which is a downstream marker of Hippo signal, is increased in culture real-time PCR in which LPA and thrombin were added to a human granulosa cell line. We also confirmed the nuclear translocation of YAP.

Free Research Field

生殖工学

Academic Significance and Societal Importance of the Research Achievements

申請者等の開発したIVAは、これらの患者が自らの卵子で妊娠可能な画期的な方法であるが、2回の腹腔鏡下手術を行うため侵襲度が高く、最終的にIVF-ETが必要で自然妊娠はできない。本研究により、薬剤を用いたHippoシグナルの抑制が可能となれば、低侵襲な卵胞発育の誘導法が開発可能で、自然妊娠すらも可能となる。本法の確立で身体的にも経済的にも患者への負担が非常に軽減され、提供卵子以外の有効な治療法がないこれらの患者の大きな福音となり、生殖医学を大きく発展させると期待される。少子化対策、医療費削減など社会的にも非常に意義が高いと考えられる。