発達期ゼブラフィッシュにおけるエストロゲン様内分泌かく乱物質の単独および複合曝露による影響評価

抄録

Estrogenic endocrine disrupting chemicals (E-EDCs) have a grave attraction globally, not only for their toxicological effects in the ecosystem but also for their significant impact on human. These chemicals are more likely to occur as a combination rather than a single stressor. However, whether and how the binary exposure to E-EDCs may induce developmental effects remains largely unknown. Here we investigated the single and binary exposure to distinct xenoestrogens, diethylstilbestrol (DES), zearalenone (ZEN) and equine estrogens (EEs) on zebrafish embryos. Significant effects on cumulative mortality, growth retardation, circulatory failure and spinal curvature were observed in DES-exposed embryos (96 hours post fertilization) at 0.3 μM, as well as ZEN at 5 μM. None of EEs exhibited apparent developmental toxicity even at high concentration. Developmental toxicity of DES was improved by co-exposure to either ZEN or EEs such as equilin, equilenin, and 17α-/17β-dihydroequilenins in a concentration-dependent manner, whereas ZEN-induced toxicity was not improved by co-exposure to EEs. Additionally, DES- and ZEN-induced toxicity was counteracted by co-exposure to an estrogen receptor (ER) antagonist, indicating that ERs are involved in the developmental toxicity of single exposure. Furthermore, our results showed that co-exposure to either ZEN or EEs suppress the transcriptional expression of cyp19a1b and 17β-hsd in comparison to DES alone. These results indicate that the competitive action against the ERs could be the main mechanism of ameliorative effect posed by ZEN and EEs.