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首页> 外文期刊>Reproductive toxicology >Resveratrol, a natural aryl hydrocarbon receptor antagonist, protects sperm from DNA damage and apoptosis caused by benzo(a)pyrene.
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Resveratrol, a natural aryl hydrocarbon receptor antagonist, protects sperm from DNA damage and apoptosis caused by benzo(a)pyrene.

机译：白藜芦醇是一种天然的芳烃受体拮抗剂，可保护精子免受苯并（a）caused引起的DNA损伤和细胞凋亡。

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摘要

Benzo(a)pyrene (BaP), an aryl hydrocarbon receptor (AhR) ligand present in cigarette smoke and car exhaust, is thought to have negative effects on male reproduction. We hypothesized that BaP damages sperm through AhR activation, phase I enzyme induction, DNA adduct formation, and increased germ cell apoptosis in the testis, and that resveratrol, a natural competitive inhibitor of the AhR found in some red wines, could prevent the adverse effects of BaP on sperm. Male Balb C mice were injected subcutaneously (s.c.) for 5 weeks with a range of BaP doses (0.5 mg/kg to 50 mg/kg). Live sperm were obtained from the vas deferens, counted, and stained to measure annexin-V positive (apoptotic) cells. In a subsequent study, mice were injected for 5 weeks with corn oil (control), BaP (5 mg/kg/week), or BaP plus resveratrol (50 mg/kg/week) (n = 3 per group). Immunohistochemistry (IHC) was performed on testis sections for the determination of CYP1A1, BaP diol epoxide (BPDE) DNA adducts, and apoptosis and the results quantified by using the HSCORE, a semiquantitative scoring system. Our results demonstrated that sperm counts after 5 weeks were inversely correlated to BaP dosage. BaP (0.5 to 5 mg/week) positively correlated with sperm apoptosis while higher doses increased sperm necrosis. CYP1A1 protein was observed mainly in interstitial cells of some testis sections, but there was no significant induction by BaP. BPDE DNA adducts were induced in all components of the seminiferous tubules by BaP and suppressed by resveratrol: median HSCORE (interquartile range) control 61 (52-71.5); BaP 213 (192-248), P = 0.01 compared to control; BaP plus resveratrol 83 (70-90). BaP significantly increased apoptosis, mainly in spermatogonia: medain HSCORE (interquartile range) BaP 189 (161-223) versus control 83 (57-93), P < 0.01; and this effect was abrogated by resveratrol. Median HSCORE for BaP plus resveratrol was 112 (range 99-121). In summary, BaP caused increased sperm cell BPDE DNA adduct formation and apoptosis in the mouse. The natural AhR antagonist, resveratrol diminished BaP-induced DNA adducts and apoptosis in seminiferous tubules.
机译：香烟烟雾和汽车尾气中存在的芳基烃受体（AhR）配体苯并（a）re（BaP）被认为对男性生殖有负面影响。我们假设BaP通过AhR激活，I期酶诱导，DNA加合物形成和睾丸中生殖细胞凋亡的增加来破坏精子，而白藜芦醇（一种在某些红酒中发现的AhR的天然竞争性抑制剂）可以防止不良反应BaP对精子的影响。将雄性Balb C小鼠皮下（s.c.）皮下注射一系列BaP剂量（0.5 mg / kg至50 mg / kg）5周。从输精管获得活精子，计数并染色以测量膜联蛋白-V阳性（凋亡）细胞。在随后的研究中，给小鼠注射玉米油（对照组），BaP（5 mg / kg /周）或BaP加白藜芦醇（50 mg / kg /周）5周（每组n = 3）。在睾丸切片上进行免疫组织化学（IHC）测定CYP1A1，BaP二醇环氧化物（BPDE）DNA加合物和细胞凋亡，并使用半定量评分系统HSCORE对结果进行定量。我们的结果表明，5周后精子计数与BaP剂量成反比。 BaP（0.5至5 mg /周）与精子凋亡呈正相关，而更高剂量则可增加精子坏死。 CYP1A1蛋白主要在部分睾丸间质细胞中观察到，但BaP无明显诱导作用。 BaP可以在生精小管的所有组件中诱导BPDE DNA加合物，白藜芦醇可抑制BPDE DNA加合物：HSCORE（四分位间距）中位对照61（52-71.5）; BaP 213（192-248），与对照组相比，P = 0.01; BaP加白藜芦醇83（70-90）。 BaP显着增加了细胞凋亡，主要在精原细胞中：medain HSCORE（四分位间距）BaP 189（161-223）与对照组83（57-93），P <0.01;白藜芦醇消除了这种作用。 BaP加白藜芦醇的平均HSCORE为112（范围99-121）。总之，BaP引起小鼠精子细胞BPDE DNA加合物的形成和凋亡增加。天然的AhR拮抗剂白藜芦醇减少了BaP诱导的DNA加合物和曲细精管的凋亡。

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