Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Shuangqing RD 18, Beijing, 100085, China.
Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Shuangqing RD 18, Beijing, 100085, China.
Environ Pollut. 2020 Oct;265(Pt A):115077. doi: 10.1016/j.envpol.2020.115077. Epub 2020 Jun 22.
In the present study, the endocrine toxicity of LCT and PBA was investigated through exposure to Eremias argus for two weeks under environmental relevant concentration. RNA-sequencing identified 4442 and 4653 differentially expressed genes in lizard liver after LCT and PBA exposure. Four differentially expressed genes (hsd17β, ar, sult, ugt) related with hypothalamic-pituitary-gonadal axis were quantified by qPCR. The expression of genes associated with HPG axis in different tissues differed significantly. In LCT treatment group, ar, cyp17 and hsd3β genes involved in testosterone synthesis and transportation were significantly decreased in lizard testes, and the spermatogensis was inhibited in the testes, which indicated the anti-androgenic activity of LCT. After PBA exposure, the genes related with estradiol synthesis, transportation and metabolism, such as hsd17β, erα, ugt in lizard liver were important biomarkers and the significant decrease of estradiol level was highly correlated with hsd17β, erα, ugt gene expressions. The relative high binding affinity of PBA with ERα further demonstrated the anti-estrogenic activity of PBA. Our results elucidate the different toxic mechanism of LCT and PBA on lizard endocrine system at environmental relevant concentration. Pyrethroids metabolism may cause more seriously toxicity rather than detoxification.
在本研究中，通过在环境相关浓度下暴露于 Eremias argus 两周，研究了 LCT 和 PBA 的内分泌毒性。RNA 测序鉴定出蜥蜴肝脏中 LCT 和 PBA 暴露后分别有 4442 和 4653 个差异表达基因。通过 qPCR 对与下丘脑-垂体-性腺轴相关的 4 个差异表达基因（hsd17β、ar、sult、ugt）进行了定量。不同组织中与 HPG 轴相关的基因表达差异显著。在 LCT 处理组中，参与睾酮合成和转运的基因 ar、cyp17 和 hsd3β 在蜥蜴睾丸中显著降低，精子发生受到抑制，表明 LCT 具有抗雄激素活性。暴露于 PBA 后，与雌二醇合成、转运和代谢相关的基因，如 hsd17β、erα、ugt 在蜥蜴肝脏中作为重要的生物标志物，雌二醇水平的显著降低与 hsd17β、erα、ugt 基因的表达高度相关。PBA 与 ERα 具有相对较高的结合亲和力进一步证明了 PBA 的抗雌激素活性。我们的研究结果阐明了 LCT 和 PBA 在环境相关浓度下对蜥蜴内分泌系统的不同毒性机制。拟除虫菊酯的代谢可能会导致更严重的毒性，而不是解毒。
