• 关键词：TCDD  NIH小鼠  早期妊娠毒性  生殖激素

• 基金项目：国家自然科学基金资助项目(30371196)

• 黄莉
• 1. 广州医学院实验动物研究中心, 广州 510182; 2. 西北农林科技大学, 杨凌 712100

• 王建华
• 西北农林科技大学, 杨凌 712100

• 戴丽军
• 广州医学院实验动物研究中心, 广州 510182

• 邱剑峰
• 广州医学院实验动物研究中心, 广州 510182

• 吕嘉春
• 广州医学院化学致癌研究所, 广州 510182

• 李冰
• 广州医学院实验医学研究中心, 广州 510182

• 摘要：用不同剂量的2,3,7,8-四氯苯二英(2,3,7,8-tetrachlorodibenzopdioxin,TCDD)对小鼠胚胎附植数量和生长发育情况进行剂量反应评估,分析TCDD对假孕小鼠子宫蜕膜生长状况的影响以及比较胚胎种植前后染毒效果.所有样本采集血液,测定母体血清雌二醇和孕酮的浓度变化.结果表明,50和100ng·(kg·d)^-1TCDD处理的孕鼠,胚胎附植数量明显减少(P<0.05),着床后胚胎出现发育迟缓,质量减轻(P<0.05);同等剂量TCDD处理的假孕小鼠,子宫蜕膜生长受到了极显著的抑制(P<0.01);种植前后染毒效果比较发现种植前期染毒的小鼠胚胎对TCDD更为敏感.母体血清雌二醇浓度随剂量和染毒时段有不同程度的升高,而孕酮浓度则极显著下降(P<0.01).由此表明低剂量TCDD可能通过对生殖激素的干扰,强烈影响NIH小鼠妊娠早期生殖生理状态和着床后胚胎的发育.实验同时证明小鼠也可作为早期妊娠毒物研究的供试动物,用以筛选动物和人类早期妊娠的有害化合物.

• Abstract：The effects of 2,3,7,8-tetrachlorodibenzopdioxin (TCDD)on the implantation and early development of embryo in NIHmice were investigated. According to the Early Pregnancy Protocol of toxic chemical screening, groups of pseudo-pregnant and pregnant NIHmice were dosed orally with TCDDof 0, 2.0, 50 and 100ng·kg^-1·d^-1 on Days 1~8,1~3 and 4~8 of early pregnancy. The animals were sacrificed on day 9 of pregnancy, the numbers of embryo implantation sites, the weight of embryo and the weight of the uterus of pseudo-pregnant mice were recorded for the Dose Response Evaluation, the Decidual Cell Response and the Pre-versus Post-implantation Analysis. The serum was also collected for evaluating the estrogen and progesterone levels on day 9. The results showed that the number of implantation sites decreased significantly(P<0.05) with the occurrence of post-implant embryo death and retardation of embryo development when the mice were dosed with 50 and 100ng·kg^-1·d^-1 TCDD. And this treatment inhibited uterus deciduas growth of pseudo-pregnant mice significantly (P<0.01). Pre-versus Post-implantation analysis revealed that pre-implantation stage was more sensitive than post-implantation stage. Various doses of TCDDtreatment induced the increasing of cycling estrogen level with different significance, and the decreasing of cycling progesterone level very significantly (P<0.01). The results explicated that TCDDexerted the harmful effects on pregnancy of NIHmouse at very early stage,and cycling reproductive hormone levels disturbed by TCDDmight be responsible for the early loss of embryos. The effective TCDDdosage is lower than reported, possibly due to the sensitivity of NIHmouse. The results also demonstrated that mouse system could be used to screening the chemicals effecting early pregnancy of animals and human.

• Key words：TCDD, NIH mouse  early pregnancy protocol  reproductive hormones

• 
  摘要点击次数： 1911 全文下载次数： 2856