胚胎植入期二硫化碳染毒对孕鼠血清雌激素及子宫雌激素受体-α表达的影响

Effects of carbon disulfide exposure during peri-implantation on estrogen receptor-α expression in uterus and serum level of estrogen in pregnant mice

目的观察胚胎植入期二硫化碳（Cs2）暴露对孕鼠血清雌二醇（E2）含量和子宫组织雌激素受体d（ER-α）表达水平的影响，探讨Cs2致胚胎毒性的作用机制。方法健康雌性小鼠分别在受孕后第3天（GD3）、第4天（GD4）、第5天（GD5）、第6天（GD6）暴露于单一剂量（631．4mg／kg）的CS2或橄榄油（溶剂对照），单次暴露之后在不同的观察终点结束实验。采用酶联免疫吸附试验（ELISA）检测各观察终点孕鼠血清E2含量，采用十二烷基磺酸钠-聚丙烯酰胺凝胶电泳（SDS）和蛋白免疫印迹法（Western blotting）检测各观察终点子宫组织ER-α表达水平。结果GD3、GD4、GD5和GD6各暴露组在孕后第7天观察终点血清E2水平有不同程度的下降，差异均有统计学意义（P〈0．05）；GD3和GD5暴露组孕鼠在孕后第6天观察终点其血清E2水平也有所下降，差异有统计学意义（P〈0．05）。Western blotting结果显示，GD4和GD5暴露组孕鼠子宫组织中ER-α均在暴露后第一个观察终点（即孕后第5天和孕后第6天）低表达，表达水平分别较对照组降低了23．6％和72．9％，差异均具有统计学意义（P〈0．05）；GD3和GD6暴露组孕鼠在各观察终点ER-α表达水平均较对照组有所降低，但差异无统计学意义（P〉0．05）。结论胚胎植入期Cs2暴露可降低子宫组织ER-α表达水平并减少孕鼠血清E2含量，这可能是Cs2致胚胎毒性的分子机制之一。

Objective Toevaluate the effects ofcarbon disulfide （CS2） exposure during peri-implantation on the estrogen receptor-α （ER-α） expression in the uterus and serum level of estradiol （E2） in pregnant mice, and to explore the mechanism of embryotoxicity of CS2. Methods Healthy female mice were exposed to a single dose of CS= （631.4 mg/kg） or olive oil （solvent control） on gestational day （GD）3, GD4, GD5, or GD6. At different time points after exposure, the serum E2 levels of the pregnant mice were measured by enzyme- linked immunosorbent assay, and the expression levels of ER-α in the uterus were measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot. Results Compared with the control group, the GD3, GD4, GD5, and GD6 exposure groups showed significantly decreased serum E2 levels on day 7 of gestation （P〈0.05）; the GD3 and GD5 exposure groups showed significantly decreased serum E2 levels on day 6 of gestation （P〈0.05）. The expression level of ER-α in the GD 4 exposure group was 23.6% lower than that in the control group on day 5 of gestation, and the expression level of ER-α in the GD 5 exposure group was 72.9% lower than that in the control group on day 6 of gestation （P〈0.05）; the GD 3 and GD 6 exposure groups showed lower expression levels of ER-α than the control group at any time point, but no significant difference was found （P〉0.05）. Conclusion CS2 exposure during peri-implantation can reduce the ER-α expression in the uterus and the serum level of E2 in pregnant mice, which may be one of the mechanisms of embryotoxicity of CS2.