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首页> 外文期刊>Toxicological sciences: An official journal of the Society of Toxicology >Bisphenol A exposure induces apoptosis and upregulation of Fas/FasL and caspase-3 expression in the testes of mice.
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Bisphenol A exposure induces apoptosis and upregulation of Fas/FasL and caspase-3 expression in the testes of mice.

机译:双酚A暴露可诱导小鼠睾丸的凋亡以及Fas / FasL和caspase-3表达的上调。

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摘要

There are controversies about adverse effects of bisphenol A (BPA), a ubiquitous xenoestrogen, on reproduction and development of male animals. To understand BPA action and assess its risk more completely, we examined the impact of BPA at high doses on the testes of pubertal male Kunming (China) mice. BPA at 0 (control), 160, 480, and 960 mg/kg/day was given by gavage to mice from postnatal days (PND) 31-44, followed by observation of morphology and detection of apoptosis and expressions of Fas/FasL and active caspase-3 on PND 45, 60, and 90 by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling, immunohistochemistry, and Western blotting. There was no effect of BPA at 160 mg/kg/day, however, at 480 and 960 mg/kg/day there was underdevelopment of testes and disruption of spermatogenesis. There were many apoptotic Leydig and germ cells in the testes with apoptotic indices being significantly increased compared with controls. The expression of Fas and active caspase-3 was localized in the same cell types as apoptosis occurred, and expression levels of Fas, FasL, and active caspase-3 were significantly increased compared with controls. The disturbed spermatogenesis, apoptosis and upregulation of Fas, FasL, and active caspase-3 expression persisted to PND 90. The results suggest that high-dose BPA induces apoptosis of Leydig and germ cells in the mouse testis through the Fas-signaling pathway. Therefore, there is concern about reproductive health for humans occupationally exposed to high levels of BPA.
机译:关于双酚A(BPA)(一种普遍存在的异种雌激素)对雄性动物生殖和发育的不利影响存在争议。为了了解BPA的作用并更全面地评估其风险,我们检查了高剂量BPA对青春期雄性昆明(中国)小鼠睾丸的影响。从出生后(PND)31-44开始对小鼠灌胃0(对照),160、480和960 mg / kg / day的BPA,随后观察形态学并检测凋亡以及Fas / FasL和FasL的表达通过末端脱氧核苷酸转移酶(TdT)介导的dUTP缺口末端标记,免疫组织化学和Western印迹检测PND 45、60和90上的Caspase-3活性。 BPA在160 mg / kg / day时没有作用,但是在480和960 mg / kg / day时睾丸发育不佳,精子发生受到破坏。睾丸中有许多凋亡的Leydig和生殖细胞,与对照组相比,凋亡指数显着增加。 Fas和活性caspase-3的表达定位在与凋亡相同的细胞类型中,与对照相比,Fas,FasL和活性caspase-3的表达水平显着增加。 Fas,FasL和活跃的caspase-3表达的精子发生,凋亡和上调受到干扰一直持续到PND90。结果表明,大剂量BPA通过Fas信号传导途径诱导小鼠睾丸间质细胞和生殖细胞凋亡。因此,对于在职业中暴露于高水平BPA的人类的生殖健康存在关注。

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