BPA、DES及联合暴露对雄性大鼠生殖毒性的研究

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目的研究低剂量双酚A(Bisphenol A,BPA)、己烯雌酚(Diethylstilbestrol,DES)及两者联合暴露对雄性SD大鼠的生殖毒性。方法选择健康的雄性SD大鼠35只,随机分成7组,分别用0.5、5 mg/kg BPA,0.05、0.5μg/kg DES,以及0.5 mg/kg BPA+0.05μg/kg DES、5 mg/kg BPA+0.5μg/kg DES进行灌胃染毒,观察记录大鼠的体重变化,在染毒4周时处死取材。取大鼠两侧睾丸和附睾并称重,检测精子活力水平;做睾丸组织病理学切片,观察睾丸组织形态变化;检测血清激素水平。结果 BPA、DES及联合染毒4周后,联合暴露高剂量组的体重增重程度显著高于对照组(P<0.05),附睾质量显著低于对照组(P<0.05),睾丸质量有下降的趋势。联合暴露高剂量组的快速游动精子百分比显著增高(P<0.05),DES低剂量组和联合暴露高剂量组的慢速游动精子百分比均显著降低(P<0.05),BPA高剂量组、DES组和联合暴露低剂量组不动精子百分比显著增加(P<0.05)。染毒组大鼠生精细胞和支持细胞分离,细胞排列疏松紊乱,可见少量生精细胞空泡化,且联合暴露组病理学改变程度最大。血清睾酮水平,BPA高剂量组和联合暴露高剂量组显著高于对照组,联合暴露低剂量组显著低于对照组(P<0.05)。结论低剂量BPA和DES对大鼠有一定的生殖毒性,两者联合暴露对大鼠体重、附睾质量、精子活力和激素水平等的影响更显著,睾丸组织形态出现病变也更严重。 Objective To study the reproductive toxicity of low dose bisphenol A (BPA), diethylstilbestrol (DES) and their combined exposure on male SD rats. Methods Thirty-five healthy male Sprague-Dawley rats were randomly divided into 7 groups: 0.5 mg / kg BPA, 0.05,0.5 μg / kg DES and 0.5 mg / kg BPA plus 0.05 μg / kg BPA + 0.5μg / kg DES were administered intragastrically. Changes in body weight of rats were observed and sacrificed at 4 weeks after exposure. Testis and epididymis on both sides of rats were weighed and weighed, and the level of sperm motility was measured. Testis histopathological sections were made to observe the morphological changes of testis and serum hormone levels were measured. Results Compared with the control group (P <0.05), the body weight gain of the high-dose combined exposure group was significantly lower than that of the control group (P <0.05) and the testicular weight was decreased the trend of. (P <0.05). The percentages of slow motile spermatozoa in DES low-dose group and combined high-dose exposure group were significantly decreased (P <0.05). The high-dose BPA group, The percentage of fixed sperm in DES group and low exposure group were significantly increased (P <0.05). The germ cells and supporting cells of the rats in the exposure group were separated and the cells were loosely arranged. A small amount of germ cells were observed to be vacuolized, and the pathological changes of the combined exposure group were the largest. The levels of serum testosterone, BPA high-dose group and high-dose combined exposure group were significantly higher than those of the control group, and the low-dose combined exposure group was significantly lower than that of the control group (P <0.05). Conclusion Low doses of BPA and DES have some reproductive toxicity to rats. The combined effects of the two drugs have significant effects on body weight, epididymis quality, sperm motility and hormone levels, and the pathological changes of testes are more serious.
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