AOPレポート: 発育性アンドロゲンシグナル伝達阻害による不良結果経路ネットワーク
Terje Svingen1, Emilie Elmelund1, Marie L Holmer1
1National Food Institute, Technical University of Denmark, Kgs. Lyngby, DK-2800Denmark.
Environmental toxicology and chemistry
|September 1, 2025
まとめ
胎児の発達中のアンドロゲンシグナル伝達の減少は,雄性哺乳類の陰茎距離 (AGD) を短縮する可能性があります. この有害な結果経路ネットワーク (AOPN) は,分子イベントとAGDの減少を結びつけ,化学的リスクの評価を助けます.
科学分野:
- 毒理学について
- 発達生物学
- 内分泌学
背景:
- アノゲニタル距離 (AGD) は,哺乳類における性二形態的特徴であり,抗アンドロゲン化学物質の露出を評価するために重要である.
- 胎児の発達中のアンドロゲンシグナル伝達が減少することは,男性におけるAGDの短い原因として知られています.
- AGD測定はOECDの生殖毒性試験で確立されたエンドポイントです.
研究 の 目的:
- 減少した胎児のアンドロゲンシグナル伝達と短縮されたAGDを結びつける有害結果経路ネットワーク (AOPN) を概説する.
- 抗アンドロゲン化学物質の危険とリスクの評価のためのメカニズム的なリンクを記述する.
- 予測毒理学における非動物実験データの利用を容易にする.
主な方法:
- 減少したAGDに収束する3つの異なる有害結果経路 (AOPs) を含むAOPNの開発.
- 新しいイベントを含むキーイベント (KE) とキーイベント関係 (KER) の特定と統合 (KE 2298,KER 2127,3448,3449,3349)
- AOPs 305,306,307の評価は,主にマウス,ラット,ヒトの研究からの証拠を用いて行われました.
主要な成果:
- AOPNは,アンドロゲンシグナル伝達に影響する分子発起イベントを,減少したAGDの悪影響と成功裏に結びつけています.
- アップストリームKEsとKERは,哺乳類に広く適用され,in vitro方法で測定できます.
- ダウンストリームイベントは,男性の子孫の部発達とAGDに焦点を当てており,AOPには中等から高い信頼性があります.
結論:
- 開発されたAOPNは,抗アンドロゲン暴露の効果を理解し予測するための堅固な枠組みを提供します.
- このネットワークは,化学安全性評価のためのメカニズムデータと in vitro 方法の使用をサポートします.
- 発見は哺乳類と潜在的に他の脊椎動物にとって広範な分類学的な関連性を持っています.
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