Adverse outcome pathway network approach to identify endocrine disruptor-induced reproductive toxicity

Endocrine-disrupting chemicals (EDCs) can cause reproductive toxicity in both humans and animals. To study this reproductive toxicity, extensive efforts have been made to determine the mode of action (MoA) of EDCs of interest, which typically act in complex chemical settings. Recently, notable progress has been made in computational tools in this field, owing to their high reliability, efficiency, and accessibility. The adverse outcome pathway (AOP) network is one of the most representative tools for investigating all possible pathways of reproductive toxicity caused by EDCs in a complex environment. In this review, we aimed to provide a guide for the implementation of an AOP network for evaluating EDC-induced reproductive toxicity. Specifically, we introduce the principles for establishing an AOP network, present widely used software and toolboxes for constructing an AOP network, and discuss a few successful cases of reproductive toxicity induced by EDCs using the AOP network. Future development of a quantitative AOP network is proposed.