2,3,7,8-四氯苯并二噁英(TCDD)短期染毒可造成着床前胚胎丢失并伴随雌性生殖器官中毒物相关蛋白的诱导表达  

Short Time Exposure of TCDD Causing Loss of Implantation Failure of Embryos and Its Associated with Induced Expression of Relevant Proteins

作　　者：黄莉[1] 黄韧 冯媛瑜[1] 刘寒英[1] 丘剑峰[1] 李冰[3] 

机构地区：[1]广州医学院实验动物研究中心,广州510182 [2]广东省实验动物检测所,广州510260 [3]广州医学院实验医学研究中心,广州510182

出　　处：《生态毒理学报》2010年第3期334-342,共9页Asian Journal of Ecotoxicology

基　　金：广东省实验动物重点实验室开放课题基金(No.2007A060101002);广州医学院课题基金(No.2006ZR003)

摘　　要：为探明妊娠早期胚胎的丢失是否与卵巢、输卵管、子宫组织受到2,3,7,8-四氯苯并二噁英(TCDD)直接毒害有关,检测了NIH小鼠胚胎着床前期和后期TCDD暴露对胚胎毒性影响的敏感性,并利用免疫组化方法分析了模型动物肝脏、子宫、输卵管和卵巢组织中TCDD所引起的AhR、ARNT以及Cyp1a2分子标记物的变化.检测发现:妊娠第9d,100ng·kg-1·d-1剂量TCDD经口染毒,造成胚胎着床数量减少,且着床前期暴露的影响大于着床后期;子宫蜕膜反应受到明显抑制;胚胎迁移率没有明显变化,但胚胎数量减少.免疫组织化学分析发现正常组小鼠的肝脏、子宫、输卵管和卵巢组织中有AhR和Cyp1a2弱阳性信号表达,ARNT有细胞核的强阳性信号表达;妊娠第1～8d、第1～3d和第4～8d处理组小鼠肝脏、子宫、输卵管和卵巢组织中的AhR、Cyp1a2的阳性面积和光密度值均高于正常组;随处理时间和组织蓄积量的增加,ARNT在组织中的变化由胞核(妊娠第1～3d组)表达到胞浆(妊娠第4～8d组)表达,然后完全无表达(妊娠第1～8d组).以上研究结果表明:TCDD对早期妊娠小鼠子宫、输卵管和卵巢组织中的AhR、ARNT和Cyp1a2的激活和代谢方式与肝脏相同,说明雌性生殖系统中的组织有TCDD蓄积和代谢活性,这可能是导致早期胚胎迁移、着床等过程改变,造成胚胎丢失的重要原因.The influence of the female reproductive organ exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin（TCDD）on the embryo lost were investigated.The Pre-（d1~3）and Post-（d4~8）implantation of TCDD exposure assay was utilized to analyze the sensitive window of embryo toxic effect in early pregnancy of NIH mice.The relevant proteins in mediating TCDD’s toxic effects including AhR,ARNT and Cyp1a2 from liver,uterus,oviduct and ovary tissues were examined by immunochemistry staining.Results showed that oral exposure of 100ng·kg-1·d-1 TCDD during Pre-implantation caused remarkable decrease of embryos of pregnant mice at day 9 of pregnancy,in contrast to that of Post-implantation exposure.In both Pre- and Post-implantation TCDD exposed mice,the decidua reaction of uterus were significantly inhibited,however,no transport rate change was observed.Weak AhR and Cyp1a2 positive signals were found in the cell plasma,and strong ARNT positive signal was found in the nuclear of all unexposed animal tissues examined.TCDD exposing groups showed increased positive signals both in area and intensity of AhR and Cyp1a2.While that of ARNT decreased in nuclear,but showed increased in plasma,and in groups with long exposure,vanished at all.It can be concluded that the relevant toxic mediating proteins in uterus,oviduct and ovary are behaving in the same way as in liver tissue,which are believed to be the major TCDD metabolism organ for activating and storing.The results can provide evidence for the hypothesis of the reproductive organ may play an important role in TCDD processing in vivo,active TCDD in these organs may directly exert hazardous effect on the early development of embryos and causing implantation failure.

关 键 词：2 3 7 8-四氯苯并二噁英(TCDD) 胚胎丢失 毒性介导蛋白 

分 类 号：R994.6[医药卫生—毒理学]