The average age for pubertal onset in girls has declined over recent decades. Epidemiological studies in humans and experimental studies in animals suggest a causal role for Endocrine Disrupting Chemicals (EDCs) that are present in our environment. Of concern, current testing and screening regimens are inadequate in identifying EDCs that may affect pubertal maturation, not least because they do not consider early-life exposure. Also, the causal relationship between EDC exposure and pubertal timing is still a matter of debate. To address this issue, we have used current knowledge to elaborate a network of putative Adverse Outcome Pathways (pAOPs) to identify how chemicals can affect pubertal onset. By using the AOP framework, we highlight current gaps in mechanistic understanding that needs to be addressed and simultaneously point towards events causative of pubertal disturbance that could be exploited for alternative test methods. We propose six pAOPs that could explain the disruption of pubertal timing by interfering with the central hypothalamic trigger of puberty, GnRH neurons, and by so doing highlight specific modes of action that could be targeted for alternative test method development.


中文翻译：

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一个假定的不良结果通路网络，用于干扰女性青春期发病，以改善内分泌干扰化学品的检测和调节

近几十年来，女孩青春期开始的平均年龄有所下降。人类流行病学研究和动物实验研究表明，我们环境中存在的内分泌干扰物 (EDC) 具有因果关系。令人担忧的是，目前的检测和筛查方案不足以识别可能影响青春期成熟的 EDC，尤其是因为它们没有考虑生命早期的暴露。此外，EDC 暴露与青春期时机之间的因果关系仍然存在争议。为了解决这个问题，我们利用现有知识详细阐述了一个假定的不良结果通路 (pAOPs) 网络，以确定化学品如何影响青春期发病。通过使用 AOP 框架，我们强调了目前需要解决的机械理解方面的差距，同时指出了可用于替代测试方法的青春期障碍的原因。我们提出了六种 pAOP，它们可以通过干扰青春期的中枢下丘脑触发器、GnRH 神经元来解释青春期时间的中断，并通过这样做突出可能针对替代测试方法开发的特定作用模式。