Reproductive effects linked to DNA methylation in male zebrafish chronically exposed to environmentally relevant concentrations of di-(2-ethylhexyl) phthalate
Reproductive effects linked to DNA methylation in male zebrafish chronically exposed to environmentally relevant concentrations of di-(2-ethylhexyl) phthalate
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长期暴露于环境相关浓度邻苯二甲酸二(2-乙基己基)酯的雄性斑马鱼的生殖影响与 DNA 甲基化有关
DOI：
10.1016/j.envpol.2017.11.025
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发表时间：
2018-06-01
影响因子：
8.9
通讯作者：
Pei, De-Sheng
中科院分区：
文献类型：
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作者：
Ma, Yan-Bo;Jia, Pan-Pan;Pei, De-Sheng
邻苯二甲酸二-（2-乙基己基）酯（DEHP）具有干扰哺乳动物雄性生殖内分泌系统的潜力；然而，其对雄性斑马鱼的生殖毒性及其相关的表观遗传学研究尚未深入研究。本研究以3月龄雄性斑马鱼为研究对象，连续3个月暴露于环境相关浓度（0、10、33和100 μ g/L）的DEHP环境中，研究DEHP对雄性繁殖的影响及其机制。组织学检测显示，暴露浓度为100 μ g/L的DEHP可显著抑制精子发生，并导致未处理卵母细胞受精能力下降。电镜检查还显示，在100 μ g/L DEHP暴露水平下，睾丸超微结构明显受损。此外，暴露于33和100 μ g/L DEHP导致循环睾酮(T)下降，17 β -雌二醇（E2）水平升高，这可能与性腺中cypl7a1和hsd1763基因下调和cyp19a1a基因上调有关。这些基因的DNA甲基化状态在其启动子区域内发生改变。在较高浓度的DEHP暴露下，雄性睾丸及其后代幼虫的DNA甲基化显著增加。我们的研究结果表明，暴露于环境相关浓度的DEHP会损害睾丸，扰乱性激素的产生，抑制精子的发生，最终损害雄性斑马鱼的繁殖。(C) 2017 Elsevier Ltd.版权所有。
Di-(2-ethylhexyl) phthalate (DEHP) possesses the potential to interfere with the male reproductive endocrine system in mammals; however, its reproductive toxicity in male zebrafish and associated epigenetic studies have not been explored. In this study, three-month-old male zebrafish were exposed to environmentally relevant concentrations of DEHP (0, 10, 33 and 100 mu g/L for 3 months, and then the impact on the reproduction of males and the underlying mechanism were investigated. Histological testing showed that an exposure concentration of 100 mu g/L DEHP significantly inhibited spermatogenesis, with an associated decline in capability to fertilize untreated oocytes. Electron microscopic examinations also revealed noticeable damage to the testicular ultrastructure at the 100 mu g/L DEHP exposure level. In addition, exposure to 33 and 100 mu g/L of DEHP resulted in a decline of circulating testosterone (T) and an increase in the level of 17 beta-estradiol (E2), both of which were possibly derived from the downregulation of cypl7a1 and hsd1763 genes and the upregulation of the cyp19a1a gene in the gonads. The DNA methylation statuses of these genes were altered within their promoter regions. A significant increase in global DNA methylation in both the male testes and their offspring larvae was observed at higher exposure concentration of DEHP. Our findings demonstrate that exposure to environmentally relevant concentrations of DEHP can damage the testes, disturbe the sex hormones production, and inhibite spermatogenesis, which ultimately impairs the reproduction of male zebrafish. (C) 2017 Elsevier Ltd. All rights reserved.