妊娠早期小鼠2,3,7,8-四氯苯并对二噁英暴露抑制生殖器官ERα表达  

Exposure to 2,3,7,8-tetrachlorinated dibenzo-p-dioxin during early pregnancy inhibit ERɑ expression in mice reproductive tissues

作　　者：黄莉[1] 刘寒英[1] 李雯[2] 丘剑峰[1] 邓小亮[3] 王维华[4] 

机构地区：[1]广州医科大学实验动物中心,广东广州510182 [2]广州市第一人民医院病理科 [3]广州医科大学实验医学中心 [4]广州医学院第三附属医院

出　　处：《毒理学杂志》2013年第5期325-331,共7页Journal of Toxicology

基　　金：国家自然科学基金(81270745);广东省自然科学基金项目(201110005438)

摘　　要：目的研究2，3，7，8-四氯苯并对二噁英（TCDD）暴露对生殖激素和其受体的影响。方法NIH小鼠妊娠早期第1—8天、胚胎着床前第1—3天和着床后第4—8天灌胃0、2、50和100ng／kg剂量TCDD，妊娠第9天测定雌激素和孕激素；称取卵巢和子宫重量；取相关组织观察组织病理学变化，并采用免疫化学方法观察芳香碳氢化合物受体（AhR）和雌激素受体（ERa）在子宫、卵巢和输卵管组织的分布。结果与正常组比较，各剂量不同时间段处理组小鼠血清雌二醇（E2）水平升高，但未达到显著水平（P〉0．05）；孕酮（PG）水平在不同剂量各时间段处理组均显著下降（P〈0．05，P〈0．001，P〈0．001）；子宫和卵巢重量降低，以50和100ng／kg剂量各时间段处理组显著（P〈0．05，P〈0．01，P〈0．001）；组织AhR和ER表达有剂量依赖的改变，表现为生殖器官组织AhR细胞阳性随暴露浓度提高而增强，ER细胞阳性随浓度提高而减弱。结论TCDD通过细胞AhR介导引起性腺组织的ERa表达下调，进而降低孕激素合成和分泌，最终导致妊娠早期卵巢和子宫重量的下降，是强烈妊娠抑制的机制。Objective To further investigate the effects of TCDD exposure on circulation estrogen level and estrogen receptor （ERa） expression during early pregnancy in mouse. Methods Pregnant NIH mice were gavaged administration with 0,2,50 and 100 ng/kg body weight of TCDD on day 1-3, 4-8 and 1-8 of early pregnancy. The mice were sacrificed on day 9 and tissues include uterus, oviduct, ovary, brain and blood were collected and weighted. The level of serum estradiol and progesterone was measured by Radioimmunoassay. The aryl hydrocarbon receptor （AhR） and estrogen receptor （ERa） expression and distribution were assayed by Immuno-histochemical assay. Results Contrast with normal groups, the serum progesterone level were decreased significantly （P 〈 0. 05, P 〈 0. 001, P 〈 0. 001 ） in all TCDD treatment groups, while the estradiol level elevated but have not reached significant level; the uterus and ovary weight decreased in 50 and 100 ng/kg of TCDD （ P 〈 0. 05, P 〈 0. 01, P 〈 0. 001 ） expose groups. The immuno-histochemical staining signal of AhR was found increased dose dependently in uterus, oviduct and ovary tissue; while that of ERa was decreased. Conclusion TCDD exposure activate AhR, inhibit ERa expression, which in turn can decrease progesterone synthesis and excretion. The decreased weight gain of uterus and ovary, and reduce female reproductive performance during TCDD exposure are the result of ERa down-regulation .

关 键 词：NIH小鼠 TCDD暴露 生殖器官 雌激素受体 

分 类 号：X503.22[环境科学与工程—环境工程]