Protective effects of sulforaphane on di-n-butylphthalate-induced testicular oxidative stress injury in male mice offsprings via activating Nrf2/ARE pathway.
Protective effects of sulforaphane on di-n-butylphthalate-induced testicular oxidative stress injury in male mice offsprings via activating Nrf2/ARE pathway.
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萝卜硫素通过激活Nrf2/ARE通路对邻苯二甲酸二正丁酯诱导的雄性小鼠子代睾丸氧化应激损伤的保护作用
DOI：
10.18632/oncotarget.19981
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发表时间：
2017-10-10
期刊：
影响因子：
--
通讯作者：
Zhang W
中科院分区：
文献类型：
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作者：
Qin Z;Tang J;Han P;Jiang X;Yang C;Li R;Tang M;Shen B;Wang W;Qin C;Zhang W
邻苯二甲酸二丁酯（DBP）是最常见的内分泌干扰物之一，可干扰人体内分泌系统，尤其是男性生殖系统。本研究旨在探讨莱菔硫烷（SFN）对DBP诱导的雄性仔鼠睾丸氧化应激损伤的保护作用。从胚胎第14.5天（E）至E19.5天，对野生型（Nrf 2 +/+）和Nrf 2缺陷型（Nrf 2-/-）定时妊娠小鼠经口给予DBP。随后，对氧化应激标志物进行评价。采用免疫组化和western blot方法检测睾丸组织中Nrf 2、NF-κB、I-k B、HO-1和NQO-1的表达水平。DBP显著缩短雄性小鼠子代的肛门生殖器距离（AGD）并影响睾丸的生长，而SFN改善这些表型。DBP刺激后，睾丸形态学、睾丸细胞凋亡指数和氧化应激指标与对照组相比差异有统计学意义，而SFN补充组睾丸形态学、睾丸细胞凋亡指数和氧化应激指标与对照组相比差异有统计学意义，SFN补充组睾丸形态学、睾丸细胞凋亡指数和氧化应激指标与对照组相比差异有统计学意义。另外，SFN还能明显提高Nrf 2及其下游ARE基因组HO-1、NQO-1在睾丸中的表达水平。同时，SFN预处理并没有对DBP诱导的Nrf 2基因敲除小鼠睾丸氧化应激损伤提供保护。因此，SFN可通过Nrf 2/ARE信号通路对DBP诱导的雄性仔鼠睾丸氧化应激损伤起到保护作用。
Di-N-butylphthalate (DBP) is one of the most common endocrine-disrupting chemicals which can disrupt human endocrine system, especially in the male reproductive system. Here, this study was aimed to determine whether sulforaphane (SFN) could protect against testicular oxidative stress injury induced by DBP in male mice offsprings. Wild-type (Nrf2+/+) and Nrf2-deficient (Nrf2-/-) timed-pregnant mice were given DBP orally from embryonic day (E)14.5 to E19.5. Subsequently, the oxidative stress markers were evaluated. Besides, Nrf2, NF-κB, I-kB, HO-1 and NQO-1 expression levels in the testis were measured by immunohistochemical staining or western blot analysis. DBP significantly reduced anogenital distance (AGD) and influenced testes growth in male mice offsprings, while SFN ameliorated these phenotypes. After DBP stimulation, the testicular morphology, testicular cell apoptosis index and the oxidative stress markers exhibited statistical differences compared with Control group, while SFN supplementation showed obvious improvements. In addition, administration of SFN could obviously increase the expression level of Nrf2 and its downstream ARE gene battery, such as HO-1, NQO-1 in the testis. Meanwhile, SFN pretreatment did not confer protection against DBP-induced testicular oxidative stress injury in Nrf2 knockout mice. Therefore, the present findings suggested that SFN could effectively protect against DBP-induced testicular oxidative stress injury through Nrf2/ARE signaling pathways in male mice offsprings.