Long-term 1-nitropyrene exposure induces endoplasmic reticulum stress and inhibits steroidogenesis in mice testes
Long-term 1-nitropyrene exposure induces endoplasmic reticulum stress and inhibits steroidogenesis in mice testes
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长期接触 1-硝基芘会诱导内质网应激并抑制小鼠睾丸的类固醇生成
DOI：
10.1016/j.chemosphere.2020.126336
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发表时间：
2020-07-01
期刊：
影响因子：
8.8
通讯作者：
Xu, De-Xiang
中科院分区：
文献类型：
--
作者：
Li, Jian;Gao, Lan;Xu, De-Xiang
1-硝基芘（1-NP）是柴油机尾气中具有代表性的硝基多环芳烃。最近，我们发现母体1-NP暴露导致胎儿生长迟缓和青春期雌性后代的认知发育障碍。为了研究长期1-NP暴露对精子发生和类固醇生成的影响，雄性小鼠通过管饲法暴露于1-NP（1.0 mg/kg/天）70天。1-NP染毒组小鼠睾丸相对重量、睾丸凋亡细胞数和附睾精子数与对照组相比无显著性差异。虽然长期1-NP暴露不影响Leydig细胞的数量，但类固醇生成基因和酶，包括星星、P450 SCC、P45017 α和1713-HD，在1-NP-暴露的小鼠睾丸中下调。相应地，血清和睾丸睾酮（T）水平降低1-NP暴露的小鼠。进一步的实验表明，睾丸GRP 78的mRNA和蛋白的上调1-NP。睾丸磷酸化IRE 1 α和切片xbp-1 mRNA（IRE 1 α的下游分子）在1-NP暴露的小鼠中升高。在I-NP暴露的小鼠中，睾丸磷酸化PERK和磷酸化-eIF 2 α（PERK途径的下游分子）增加。1-NP染毒组小鼠睾丸组织中NAPDH氧化酶亚基NOX 4和氧化应激指标HO-1、MDA含量明显升高。睾丸GSH和GSH/GSSG在1-NP暴露的小鼠降低。这些结果表明，长期1-NP暴露诱导活性氧诱发的ER应激和破坏小鼠睾丸类固醇合成。(C)2020爱思唯尔有限公司保留所有权利。
1-Nitropyrene (1-NP) is a representative nitro-polycyclic aromatic hydrocarbon from diesel exhaust. Recently, we found that maternal 1-NP exposure caused fetal growth retardation and disturbed cognitive development in adolescent female offspring. To investigate long-term 1-NP exposure on spermatogenesis and steroidogenesis, male mice were exposed to 1-NP (1.0 mg/kg/day) by gavage for 70 days. There was no significant difference on relative testicular weight, number of testicular apoptotic cells and epididymal sperm count between 1-NP-exposed mice and controls. Although long-term 1-NP exposure did not influence number of Leydig cells, steroidogenic genes and enzymes, including STAR, P450scc, P45017 alpha and 1713-HD, were downregulated in 1-NP-expoed mouse testes. Correspondingly, serum and testicular testosterone (T) levels were reduced in 1-NP-exposed mice. Additional experiment showed that testicular GRP78 mRNA and protein were upregulated by 1-NP. Testicular phospho-IRE1 alpha and sliced xbp-1 mRNA, a downstream molecule of IRE1 alpha, were elevated in 1-NP-exposed mice. Testicular phosphoPERK and phospho-elF2 alpha, a downstream molecule of PERK pathway, were increased in 1-NP-exposed mice. Testicular NOX4, a subunit of NAPDH oxidase, and HO-1, MDA, two oxidative stress markers, were increased in 1-NP-exposed mice. Testicular GSH and GSH/GSSG were decreased in 1-NP-exposed mice. These results suggest that long-term 1-NP exposure induces reactive oxygen species-evoked ER stress and disrupts steroidogenesis in mouse testes. (C) 2020 Elsevier Ltd. All rights reserved.