Department of Agricultural Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan.
Institute of Environmental Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan.
J Hazard Mater. 2014 Jul 30;277:141-9. doi: 10.1016/j.jhazmat.2014.02.013. Epub 2014 Feb 18.
Letrozole (LET) is a triazole-containing drug that can inhibit the activity of cytochrome P450 aromatase. It is an environmentally emerging pollutant because of its broad use in medicine and frequent occurrence in aquifers receiving the effluent of municipal or hospital wastewater. However, the toxic impact of LET on fish populations remains unclear. We exposed medaka fish (Oryzias latipes) at an early stage of sexual development to a continuous chronic LET at environmentally relevant concentrations and assessed the endocrine disruption effects in adulthood and the next generation. LET exposure at an early life stage persistently altered phenotypic sex development and reproduction in adults and skewed the sex ratio in progeny. As well, LET exposure led to a gender-different endocrine disruption as seen by the interruption in gene expression responsible for estrogen synthesis and metabolism and fish reproduction. LET interfering with the aromatase system in early life stages of medaka can disrupt hormone homeostasis and reproduction. This potent aromatase inhibitor has potential ecotoxicological impact on fish populations in aquatic environments.
来曲唑（LET）是一种含三氮唑的药物，可抑制细胞色素 P450 芳香酶的活性。由于其在医学上的广泛应用和在接收城市或医院废水的含水层中频繁出现，它已成为一种新出现的环境污染物。然而，LET 对鱼类种群的毒性影响尚不清楚。我们在鱼类性发育的早期阶段，将其连续慢性暴露于环境相关浓度的 LET 下，评估了成年期和下一代的内分泌干扰效应。早期生活阶段的 LET 暴露持续改变了成年期的表型性别发育和繁殖，并使后代的性别比例倾斜。此外，LET 暴露导致了性别不同的内分泌干扰，表现为负责雌激素合成和代谢以及鱼类繁殖的基因表达中断。LET 在鱼类早期发育阶段干扰芳香酶系统，会破坏激素平衡和繁殖。这种强效的芳香酶抑制剂可能对水生环境中的鱼类种群产生潜在的生态毒理学影响。
