Inhibitory effects of estrogenic endocrine disrupting chemicals on fin regeneration in zebrafish are dependent on estrogen receptors

For fish and other aquatic organisms, disrupting their capacity for repair and regeneration will reduce their quality of life and survivorship in the wild. Studies have shown that 17α-ethinylestradiol (EE2), a synthetic estrogenic endocrine disrupting chemical (EEDC), can inhibit caudal fin regeneration in larval zebrafish following fin amputation. However, whether the inhibitory effects of EE2 are dependent on Estrogen Receptor (ER) remains unknown. Therefore, in this study, amputated zebrafish larvae were exposed to the ER agonist EE2 alone and in combination with the ER antagonist ICI 182,780 (ICI), and the change in regenerative capacity was determined. The inhibition of fin regeneration caused by EE2 alone (100 ng/L) was ameliorated after combination with ICI (30-300 μg/L), and these changes in regeneration-related signaling and the immune system corresponded with morphological observations, implying that the effects of EE2 on regeneration were possibly initiated by the activation of ER. Furthermore, the role of ER was confirmed with a natural ligand of ER, namely, 17β-estradiol (E2), and as expected, the effects of E2 (10, 100 and 1000 ng/L) paralleled those of EE2. In conclusion, EEDCs can disrupt the regenerative capacity in zebrafish, possibly due to the binding and activation of ERs and the consequent alteration of signaling pathways that regulate fin regeneration and immune competence. Given that EEDCs appear to be ubiquitous in the aquatic environment, the risk of these chemicals might be readdressed regarding their potential effects on tissue repair and regeneration.