Analyzing of lip cleft caused by hypoxic environment

• Project/Area Number: 16K20561
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: NAGAOKA Ryosuke 東京医科歯科大学, 歯学部附属病院, 特任助教 (30760805)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 唇裂 / 口唇口蓋裂 / マウス / 動物実験 / 低酸素 / 口唇裂 / 唇顎口蓋裂 / 先天異常 / 低酸素環境 / 顔面形成 / 外表奇形 / 妊娠マウス

Outline of Final Research Achievements

Cleft lip and palate are the most common maxillofacial congenital anomalies in humans. The causes are often mentioned as genetic factors and/or environmental factors, and the mechanism of onset is unclear. On the other hand, hypoxic conditions can be caused by sleep apnea and vasoconstrictor drugs such as nicotine. We previously revealed that mouse embryos' lip formation were inhibited by whole embryo culture system with hypoxic condition. The inhibitation induced cleft lip, one of the type of cleft lip and palate. In this our new study, pregnant mice were exposed to hypoxic environment and the effects were examined. By the examination, t was suggested that cleft lip was induced by maternal hypoxia.

Academic Significance and Societal Importance of the Research Achievements

口唇口蓋裂はヒトにおいて発症頻度が高い先天異常であり、顎顔面に生じることから治療における物理的な負担もさることながら、本人および近親者の心理的な負担も大きい。本研究は複数ある原因の内、環境的要因としての低酸素状態に着目した。マウスを用いた実験においては妊娠中に低酸素状態に曝露されることでマウス胎仔の顎顔面形成に影響することが明らかとなった。発症に関するメカニズムは他にも多数あるが、一つ一つを解明することで予防法や治療法の開発への手がかりとなり、社会的に非常に有意義であると考えられる。