Adverse Effects of Aryl Organophosphate Esters on Reproduction

Aryl organophosphate esters (AOPEs) have been widely detected in environmental media and human samples, and increasing evidence shows that AOPEs induce adverse effects on reproductive health. This Review summarizes the exposure levels, reproductive toxicity data, and underlying mechanisms of three legacy AOPEs, including triphenyl phosphate (TPHP), 2-ethylhexyl diphenyl phosphate (EHDPP), and tricresyl phosphate (TCrP). Reproduction-related nuclear receptors (RrNRs) were concluded to play important roles in the reproductive toxicity induced by AOPEs, as all three typical AOPEs and their hydroxylated metabolites elicit binding affinity to RrNRs. We further investigated the RrNRs binding ability of the other 55 emerging AOPEs (eAOPEs) through molecular docking and found most eAOPEs (54/55) showed potential binding ability to RrNRs, especially to estrogen receptor α. This Review helped us to comprehensively understand the adverse effects of AOPEs on reproduction and predict the potential health risk of eAOPEs. AOPEs are easily metabolized in organisms, and their hydroxylated metabolites even show more potency to bind RrRNs. This Review also highlights the necessity to take the contribution of hydroxylated metabolites into account in future research.