Targeting the phenolic A-ring unifies the toxicology and remediation of environmental estrogens in aquatic environments

Environmental estrogens (EEs) pose risks to aquatic ecosystems and human health through their endocrine-disrupting potential, effects that are often shaped by recurring estrogen-mimetic structural features, including the phenolic A-ring in steroidal estrogens and analogous phenolic motifs in non-steroidal EEs. These recurring structural features provide a useful, but bounded, basis for linking the hazard mechanisms of EEs to their targeted elimination in aquatic systems. This review synthesizes current evidence on EE-associated hazards and discusses how these mechanistic insights can inform elimination strategies in aquatic systems. Available studies suggest that EEs can elicit ecotoxicological effects and are associated with carcinogenesis-relevant processes, largely through receptor-mediated signaling perturbation and epigenetic dysregulation. For remediation, risk reduction depends not only on lowering aqueous concentrations but also on attenuating ER-mediated estrogenic activity, which can be achieved by chemical or biological transformation that disrupts activity-conferring phenolic features and physical sequestration that limits bioavailability. We compare biological and chemical approaches that transform or degrade estrogenic structures with physical approaches that mainly transfer EEs between phases. We further discuss challenges posed by complex pollutant mixtures, highlighting the "Trojan Horse" effect whereby co-pollutants such as microplastics may act as carriers that modify EE transport, bioavailability, and mixture toxicity, complicating both treatment performance and risk characterization. Finally, we outline research directions that emphasize hybrid treatment trains, activity-based evaluation of transformation products, and the potential of synthetic biology to enhance targeted biodegradation under environmentally relevant conditions.