Adverse Outcome Pathway on Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)

This AOP details the linkage between binding and activation of androgen receptor (AR) in females and reductions in cumulative fecundity and spawning. AR-mediated activities are among the major concerns in endocrine disruptor screening programs. Cumulative fecundity is the apical endpoint considered in the OECD 229 Fish Short Term Reproduction Assay. It is also one of several variables with demographic significance in forecasting fish population trends. Therefore, this AOP supports the use of measures of AR activation as a means to identify chemicals with potential to adversely affect fish populations. At present, this AOP is largely supported by evidence from small laboratory model fish species. While many aspects of the biology underlying this AOP are largely conserved across oviparous vertebrates, its relevance to vertebrate classes other than fish, or to fish species employing different reproductive strategies has not been established. Thus, the applicability domain should be carefully considered when evaluating fit-for-purpose.