Di (2-ethylhexyl) phthalate-induced reproductive toxicity involved in dna damage-dependent oocyte apoptosis and oxidative stress in Caenorhabditis elegans.
Di (2-ethylhexyl) phthalate-induced reproductive toxicity involved in dna damage-dependent oocyte apoptosis and oxidative stress in Caenorhabditis elegans.
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DOI：
10.1016/j.ecoenv.2018.07.066
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发表时间：
2018-11
影响因子：
6.8
通讯作者：
Jiechen Yin;Ran Liu;Zihai Jian;Dong Yang;Yuepu Pu;L. Yin;Dayong Wang
中科院分区：
文献类型：
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作者：
Jiechen Yin;Ran Liu;Zihai Jian;Dong Yang;Yuepu Pu;L. Yin;Dayong Wang
邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种广泛使用的高环境暴露水平增塑剂。DEHP是一种持久性有机污染物，对哺乳动物具有生殖和发育毒性。本文以秀丽隐杆线虫（caenorhabditis elegans）为模型生物，探讨了DEHP的生殖毒性，确定了评价DEHP. l4c生态毒理学效应的敏感性指标。通过对家蚕幼虫DEHP的LC50和幼虫数量及世代时间的变化进行评价，我们发现DEHP的LC50与toC的LC50呈正相关。elegansexceeded 100 mg / L。10 mg/L DEHP暴露显著降低了雏鸟的产卵量，但对世代时间无显著影响。1 mg/L和10 mg/L DEHP暴露组小鼠卵母细胞和远端尖端细胞（DTC）计数显示卵母细胞数量减少，单侧性腺臂凋亡细胞增多。相比之下，DTC的荧光强度无显著差异。DEHP暴露后，HUS-1蛋白的荧光分析显示HUS-1蛋白过表达。分别采用Bradford蛋白法和AP染色法检测h2o2水平和DNA损伤程度。结果表明，DEHP暴露后，h2o2水平无显著差异，但DNA损伤明显增加。此外，10 mg/L浓度的DEHP暴露显著增加凋亡相关基因cep-1、egl-1、ced-4和ced-3的表达水平，降低ced-9的表达水平。提示cep-1、egl-1、ced-4、ced-3基因促进细胞凋亡，ced-9基因抑制细胞凋亡。同时，10 mg/L浓度的DEHP暴露降低了氧化应激相关基因mev-1和gas-1的表达。mev-1和gas-1主要参与线虫氧化应激的抑制。简而言之，暴露在DEHP环境下的秀丽隐杆线虫卵母细胞数量减少，凋亡卵母细胞数量增加，这可能与氧化应激引起的DNA损伤有关。
Di-(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer with a high environmental exposure level. As a persistent organic pollutant, DEHP causes reproductive and developmental toxicity in mammals. In this paper, the reproductive toxicity of DEHP was discussed using the model organismCaenorhabditis elegansto determine the sensitivity indices for evaluating the ecotoxicological effects of DEHP.L4C. eleganslarvae to evaluate the LC50 of DEHP and the changes in brood size and generation time, we found that the LC50 of DEHP toC. elegansexceeded 100 mg/L. And 10 mg/L DEHP exposure significantly reduced the brood sizes but not the generation time. Results of oocyte and distal-tip cell (DTC) counting suggested that the number of oocytes were decreased and apoptotic cells that from the unilateral gonad arm were increased in the 1 mg/L and 10 mg/L DEHP exposed groups. In contrast, there was no significant difference in the fluorescence intensity of DTC. Fluorescence analysis of HUS-1 showed that HUS-1 protein was overexpressed after DEHP exposure. The H2O2level and DNA damage were measured by Bradford protein assay and AP staining respectively. The results showed that there was no significant difference in H2O2level after DEHP exposure, in contrast, DNA damage was increased significantly. Moreover, 10 mg/L concentration DEHP exposure significantly increased the expression levels of apoptosis-related genes cep-1, egl-1, ced-4, and ced-3 and decreased the expression levels of ced-9. It suggested that cep-1, egl-1, ced-4, and ced-3 genes promote apoptosis and the ced-9 gene inhibits apoptosis. Meanwhile, 10 mg/L concentration DEHP exposure decreased the expression of oxidative stress-related genes mev-1 and gas-1. The mev-1 and gas-1 are mainly involved in the inhibition of oxidative stress in nematodes. In short, the decreased oocyte numbers and increased apoptosis oocyte numbers inC. eleganswhen exposed to DEHP, which may involve in the DNA damage induced by oxidative stress.