Sai Linlin, Dong Zhihua, Li Ling, Guo Qiming, Jia Qiang, Xie Lin, Bo Cunxiang, Liu Yanzhong, Qu Binpeng, Li Xiangxin, Shao Hua, Ng Jack C, Peng Cheng
Shandong Academy of Occupational Health and Occupational Medicine, Ji'nan, Shandong, China.
The 404th Hospital of PLA, Weihai, Shandong, China.
Chemosphere. 2016 Sep;159:145-152. doi: 10.1016/j.chemosphere.2016.05.008. Epub 2016 Jun 9.
As a widely used herbicide, atrazine (AZ) has been extensively studied for its adverse effects on the reproductive system, especially feminization in male animals. However, the relationship of gene expression changes and associated toxicological endpoints remains unclear. In this study, developing Xenopus laevis tadpoles were exposed to concentration of AZ at 0.1, 1, 10 or 100 μg/L continuously. Compared with froglets in the control group, there were no significant differences in body length, body weight, liver weight and hepatosomatic index (HSI) of males in groups treated with AZ for 90 d. At 100 μg/L AZ treatment caused a significant reduction of gonad weight and gonadosomatic index (GSI) of males (p < 0.01). In addition, AZ at all dose levels caused testicular degeneration, especially in froglets from the groups with 0.1 and 100 μg/L which exhibited U-shaped dose-response trend. We further investigated the gene expression changes associated with the testicular degeneration induced by AZ. We found that the expression of 1165 genes was significantly altered with 616 upregulated and 549 downregulated compared to the expression profile of the control animals. KEGG analysis showed that genes which were significantly affected by AZ are mainly involved in arginine and proline metabolism, cell cycle, riboflavin metabolism, spliceosome, base excision repair and progesterone-mediated oocyte maturation pathway. Our results show that AZ may affect reproductive and immune systems by interference with the related gene expression changes during the male X. laevis development. The findings may help to clarify the feminization mechanisms of AZ in male X. laevis.
作为一种广泛使用的除草剂,莠去津(AZ)对生殖系统的不良影响,尤其是对雄性动物雌性化的影响,已得到广泛研究。然而,基因表达变化与相关毒理学终点之间的关系仍不清楚。在本研究中,将发育中的非洲爪蟾蝌蚪连续暴露于浓度为0.1、1、10或100μg/L的莠去津中。与对照组的幼蛙相比,用莠去津处理90天的各组雄性蝌蚪的体长、体重、肝脏重量和肝体指数(HSI)没有显著差异。在100μg/L莠去津处理下,雄性蝌蚪的性腺重量和性腺体指数(GSI)显著降低(p<0.01)。此外,所有剂量水平的莠去津都会导致睾丸退化,尤其是在0.1和100μg/L组的幼蛙中呈现出U形剂量反应趋势。我们进一步研究了与莠去津诱导的睾丸退化相关的基因表达变化。我们发现,与对照动物的表达谱相比,1165个基因的表达发生了显著改变,其中616个上调,549个下调。KEGG分析表明,受莠去津显著影响的基因主要参与精氨酸和脯氨酸代谢、细胞周期、核黄素代谢、剪接体、碱基切除修复和孕酮介导的卵母细胞成熟途径。我们的结果表明,莠去津可能通过干扰雄性非洲爪蟾发育过程中的相关基因表达变化来影响生殖和免疫系统。这些发现可能有助于阐明莠去津在雄性非洲爪蟾中的雌性化机制。