カテコル-O-メチルトランスフェラーゼと2メトキシオエストラディオルの欠乏は,子宮内閉塞前症と関連しています
Keizo Kanasaki1, Kristin Palmsten, Hikaru Sugimoto
1Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
Nature
|May 13, 2008
まとめ
カテコル-O-メチルトランスフェラーゼ (COMT) が欠けていたマウスは,2-メトキシオエストラジオール (2-ME) の値が低いため,予兆症状を発症した. 2-MEのサプリメントは,これらの症状を逆転させ,子宮前出血症の診断および治療薬としての可能性を示唆しました.
科学分野:
- 生殖生物学 生殖生物学
- 妊産婦と胎児の医学について
- 遺伝学 遺伝学とは
背景:
- プレエクラムプシアは,高血圧,プロテイン尿,腫れによって特徴づけられる妊娠合併症です.
- 現在の理解では,胎盤低酸素と血管新生不均衡 (VEGF/PLGF/sFLT-1) が症状に寄与することを示唆しているが,そのメカニズムは不明である.
- 現存する理論は,すべての妊娠前出血症の症例を完全に説明できず,潜在的な上流分子欠陥を示唆しています.
研究 の 目的:
- カテコル-O-メチルトランスフェラーゼ (COMT) とその代謝産物2メトキシオエストラディオール (2-ME) が妊娠前出血症における役割を調査する.
- 妊娠前出血症の遺伝子マウスモデルを特定する.
- 妊娠前出血症における2-MEの診断および治療の可能性を調査する.
主な方法:
- COMT (Comt(-/-) 欠乏症の妊娠マウスを生成した.
- 妊娠したマウスのComt (((-/-) の表型を評価し,出血前症に似た特徴を調べた.
- 妊娠中のマウスに2-MEを投与し,症状,胎盤低酸素,分子マーカーに対する効果を評価した.
- 重度の出血前出血症とない女性のCOMTおよび2-ME濃度測定.
主要な成果:
- 妊娠したマウスは,2-ME.の欠如と関連した,子宮内閉症のようなフェノタイプを示した.
- 2-MEの投与は,これらのマウスの毒性なしで,すべてのプレエクラムプシアのような特徴を改善しました.
- 2-ME治療は胎盤低酸素,低酸素誘導因子-1α発現,sFLT-1上昇を抑制しました.
- 重度のプレエクラムプシアの女性では,COMTと2-MEのレベルが著しく低下しました.
結論:
- COMTの欠乏は,2-MEの減少につながり,マウスのプレエクラムプシアのようなフェノタイプを引き起こす.
- 2-MEは,妊娠前出血症の診断マーカーとしての可能性を示しています.
- 2-MEは,妊娠前出血症を予防または治療するための治療薬として機能する可能性があります.
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