Fas凋亡相关基因在双酚A诱导成年雄性大鼠生殖毒性中的作用

Roles of Fas apoptosis pathway-related genes on reproductive toxicity induced by bisphenol A in adult male rats

目的探讨Fas凋亡途径相关基因在双酚A(BPA)诱导成年雄性大鼠生殖毒性中的作用。方法 40只成年Wistar雄性大鼠随机等分为4组:溶媒对照组(玉米油)和低、中、高剂量BPA喂养组(10、50、250μg/kg·bw/d)。大鼠在喂养35周后处死,称量睾丸、附睾、肝、肾及心脏重量并计算脏器系数;观察精子形态及计算精子畸形率。采用荧光实时定量PCR(RT-PCR)测定睾丸组织中自杀相关因子(Fas/Fas-L)、天冬氨酸特异酶切的半胱氨酸蛋白酶3(Caspase-3)mRNA含量。结果高剂量BPA喂养大鼠精子畸形率以及睾丸组织中Fas-L mRNA及Caspase-3 mRNA含量高于对照组,差异均有显著性(P!0.05)。结论在BPA的人体每日容许摄入量水平下(TDI=50μg/kg·bw/d),未观察到生殖细胞损伤的效应;但长期经膳食暴露高剂量BPA(250μg/kg·bw/d)可致成年雄性大鼠生殖细胞损伤,其机制可能与BPA上调Fas-L mRNA和Caspase-3的表达有关。

Objective To explore the effect of Fas apoptosis-regulation gene on reproductive toxicity induced by bisphenol A in adult male rats. Methods Forty adult male Wistar rats were randomly divided into four groups （three exposed groups and one control group） , ten in each. The rats were fed with different doses of bisphenol A （0,10,50 and 2501.~g/kg＂ bw/d respectively） dissolved by corn oil. After 35-week treatment, the rats were sacrificed and the testis, epididymis ,liver, heart, kidney,ete were removed immediately and weighed. Moreover, sperm morphology was observed and sperm deformity rates were calculated. Real-time quantitative polymerase chain reaction （RT-PCR） was conducted to detect levels of suicide related factor （Fas/Fas-L） and aspartie acid specific enzyme of cysteine proteinase 3 （Caspase-3） mRNA in testicular tissue of rats. Results Compared with control group,the sperm abnormality rate,content of Fas-L mRNA and easpase-3 m- RNA of testis tissue in rats treated with 250 Ixg/kg＂ bw/d bisphenol A significantly increased （ P 〈0. 05 ）. Conclusions No damage effects on sperm of male treated by dose of the daily allowed intake level （50 μg/kg, bw/d） were observed, sustaining exposure to high dose of bisphenol A （250 μg/kg.bw/d） via food intaking can induce the reproductive toxicity in male rat which may be attributed to up-regulation of Fas-L and Caspase-3 mRNA levels in testis.