An adverse outcome pathway (AOP) is a simplified description of the sequence of mechanistic events that lead to a particular toxicological effect, from initial trigger to adverse outcome. Although designed to inform regulatory risk assessors, the AOP framework also provides a platform for innovative collaborations between experts from relevant research fields and the regulatory community. The underpinning for any AOP is basic knowledge about molecular and developmental processes; such knowledge can only be attained by solid bioscientific research. Starting with this fundamental knowledge, the objective is to devise novel testing strategies that focus on key events in a causative pathway. It is anticipated that such a knowledge-based approach will ultimately alleviate many of the burdens associated with classical chemical testing strategies that typically involve large-scale animal toxicity regimens. This hails from the notion that a solid understanding of the underlying mechanisms will allow the development and use of alternative test methods, including both in vitro and in silico approaches. This review is specifically targeted at professionals working in bioscientific fields, such as developmental and reproductive biology, and aims to (i) inform on the existence of the AOP framework and (ii) encourage new cross-disciplinary collaborations. It is hoped that fundamental biological knowledge can thus be better exploited for applied purposes: firstly, an improved understanding of how our perpetual exposure to environmental chemicals is causing human reproductive disease and, secondly, new approaches to screen for harmful chemicals more efficiently. This is not an instructional manual on how to create AOPs; rather, we discuss how to harness fundamental knowledge from the biosciences to assist regulatory toxicologists in their efforts to protect humans against chemicals that harm human reproductive development and function.

中文翻译：

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发育生物学与毒理学相遇：促进生殖机制建立不利的结果途径。

不良结局途径（AOP）是导致从初始触发到不良结局的导致特定毒理学作用的机械事件顺序的简化描述。尽管旨在为监管风险评估人员提供信息，但AOP框架还为相关研究领域的专家与监管界之间的创新合作提供了平台。任何AOP的基础都是有关分子和发育过程的基础知识；这些知识只能通过扎实的生物科学研究获得。从这一基础知识开始，目标是设计新颖的测试策略，重点关注因果关系中的关键事件。可以预见，这种基于知识的方法最终将减轻与经典化学测试策略相关的许多负担，这些策略通常涉及大规模的动物毒性治疗方案。这源于以下观念：对基本机制的扎实了解将允许开发和使用替代测试方法，包括体外和计算机方法。这项审查特别针对在诸如发展和生殖生物学等生物科学领域工作的专业人员，其目的是（i）告知AOP框架的存在，以及（ii）鼓励新的跨学科合作。希望可以因此将基础生物学知识更好地用于应用目的：首先，更好地了解我们长期接触环境化学物质如何导致人类生殖疾病，其次，新方法可以更有效地筛查有害化学物质。这不是有关如何创建AOP的指导手册；相反，我们讨论了如何利用生物科学的基础知识来协助监管毒理学家努力保护人类免受危害人类生殖发育和功能的化学物质的侵害。