Clinical significance of MMPs and TIMPs in pathogenesis of patients with recurrent pregnancy loss

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11100
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Nagoya City University
• Principal Investigator: Ozaki Yasuhiko 名古屋市立大学, 大学院医学研究科, 教授 (50254280)
• Research Collaborator: Goto Shinobu ; Sugiura Mayumi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 不育症 / 習慣流産 / プロテアーゼ / MMP / TIMP / 脱落膜 / 頸管粘液

Outline of Final Research Achievements

We investigated the role of MMPs and TIMPs in recurrent pregnancy loss (RPL). The expression of MMP-2 in decidua with normal chromosome group (NC) was significantly lower than in abnormal chromosome group (AC) . And the expression of MMP-9 in decidua with NC is significantly higher than in AC. The staining of MMP-2 and TIMP-2 were observed in stromal cells and in cytoplasm of only AC. MMP-9 and TIMP-1 were observed in stromal cells. Concentration of MMP-2 in plasma with APS(-) (n=10) was significantly lower than in control and MMP-9 in patients was significantly higher than control. Concentration of TIMP-1 in plasma with APS(-) was significantly lower than APS(+) . The ratio of MMP9/TIMP1 in plasma with patient was significantly higher than control and ratio of MMP2/TIMP2 in APS(-) group was significantly lower than APS(+) . These results suggested that MMPs and TIMPs play an important role in pathogenesis of RPL and that they can be one of the predictive factors in patients with RPL.

Free Research Field

医師薬学

Academic Significance and Societal Importance of the Research Achievements

不育症の約25％が原因不明であり、我々はそれらにおけるプロテアーゼの関与を検討してきた。今回の検討より、妊娠初期の脱落膜組織におけるMMP-2の発現の低下が間質における絨毛の浸潤不全を介して流産を惹起している可能性が考えられた。また好中球の活性化によるMMP-9の増加が好中球エラスターゼやカテプシンGの活性化を制御して感染性の流産病態を惹起している可能性があると思われた。また非侵襲的な不育症（流産）の予知マーカーとして、子宮頸管粘液中のMMPやTIMPの応用できる可能性を示すことができた。