邻苯二甲酸二(2-乙基己基)酯对大鼠睾丸发育及StAR、CYP19a1、CYP11a1基因表达的影响

目的通过邻苯二甲酸二(2-乙基己基)酯(DEHP)28天短期重复暴露,探讨DEHP对雄性大鼠生殖系统发育的影响及其作用机制。方法40只7～9周龄雄性Wistar大鼠分为对照组(灌胃玉米油)和低、中、高剂量染毒组(每天灌胃DEHP10、100和1000mg/kg),每组10只,动态观察动物一般状况、体重变化。28天后断头处死大鼠,测定睾丸组织脏器系数;对睾丸和附睾进行病理学观察。提取睾丸组织的总RNA,逆转录合成cDNA,通过PCR扩增产物比较DEHP不同剂量染毒对StAR、CYP19a1和CYP11a1基因表达的影响。结果随着DEHP剂量增加,大鼠体重增长受限(F=3.54,P0.05);睾丸重量及其脏器系数降低,且高剂量组与对照组相比差异有显著性(F=105.545,P0.05);DEHP可使大鼠睾丸和附睾组织结构发生病理性改变,在中、高剂量组尤为明显;RT-PCR检测表明,与对照组相比,CYP19a1及CYP11a1基因表达降低,而StAR基因表达在各组间差异无显著性。结论DEHP对青春期雄性大鼠的生殖系统发育具有明显的毒性作用,导致睾丸重量降低,发育不全。DEHP及其代谢产物可能通过影响CYP19a1和CYP11a1等芳香化酶的基因表达,干扰内分泌平衡而使青春前期雄性大鼠产生生殖系统的发育障碍。

Effect on the testis development and StAR,CYP19a1 and CYP11a1 expression of prepubertal male rats after sub-acute exposure to DEHP

Objective To study the effect of DEHP on testis development and the related gene expression in prepubertal male rats after 28 days exposure in order to explore the mechanism of genital toxicity. Methods The prepubertal Wistar rats were lavaged consecutively for 28 days with the DEHP dose of 10,100 and 1000 mg·kg -1· d -1 . The change of body weight and status were observed dynamically. After decapitation 28 days later,the organ coefficient of testis was measured. Meanwhile the morphological changes of testis and epididymis were observed by HE staining under optical microscopes. The total RNA of testis was extracted and cDNA synthesis was followed as the manual instruction of RT-PCR kit. The effect of DEHP on gene expression of StAR,CYP19a1 and CYP11a1 was compared to each other in different DEHP group. Results The body weight growth of rats in 1000 mg /kg DEHP group was restricted compared with the control (F = 3. 54,P < 0. 05). Both the weight and the organ coefficient of testis were also degraded,and there were statistical significance between the 1000 mg /kg DEHP group and the control(F = 105. 545,P < 0. 05). The serious morphological changes of testis and epididymis were shown in 100, 1000 mg /kg DEHP group. In addition,the distinct difference in the gene expression of StAR wasn’t shown in the study. On the other hand,CYP19a1 and CYP11a1 showed significant changes compared with the control due to the DEHP treatment. Conclusion DEHP could influence the expression of aromatized enzyme such as CYP19a1 and CYP11a1,and then induce genital toxicity in male rats during the developmental phase.