邻苯二甲酸二-(2-乙基)己酯致小鼠隐睾睾丸和附睾的组织病理学改变

Histopathological Changes of the Cryptorchid Testis and Epididymis of Mice Exposed to DEHP

目的 :探讨邻苯二甲酸二 (2 乙基 )己酯 (DEHP)引起的小鼠隐睾睾丸和附睾的组织病理学改变。 方法 :妊娠KM小鼠 4 0只 ,随机分成 5组 ,分别为正常对照组 8只、玉米油对照组 8只、己烯雌酚 (DES)组 8只、DEHP低剂量组 [DEHP 10 0mg/ (kg·d) ]9只和DEHP高剂量组 [DEHP 5 0 0mg/ (kg·d) ]7只。自妊娠第 12d开始到分娩后 3d ,分别持续经口给予DEHP 10 0mg/ (kg·d)、5 0 0mg/ (kg·d)和DES 10 0 μg/ (kg·d)及玉米油 ,观察仔代雄小鼠的隐睾发生率及隐睾睾丸和附睾的组织病理学改变。 结果 :DEHP 5 0 0mg/ (kg·d)组染毒小鼠的隐睾发生率显著增高 ,睾丸和附睾的体积明显减小、重量减轻 ;睾丸生精上皮发育明显异常 ,精曲小管变薄、萎缩 ,间质细胞异常增生 ,电镜下其隐睾精曲小管上皮和间质细胞均出现明显的超微结构改变。同时附睾管腔中的精子数显著减少甚至缺乏。 结论 :高剂量 [5 0 0mg/ (kg·d) ]DEHP可能具有与DES类似的作用 ,是一种诱发隐睾的重要因子。小鼠在孕期及哺乳期接触DEHP后可引起雄性仔鼠性分化异常 ,诱导隐睾发生、睾丸生精上皮损害和生精过程障碍 ,从而对雄性仔鼠生育力产生不利影响。以上作用存在明确的量 效关系。

Objective: To investigate the effects of DEHP on the incidence of cryptorchidism and the histopathological changes of the testis and epididymis in mice. Methods: Forty KM mice were divided into 5 groups randomly: normal control group(n=8), corn oil group(n=8), DES group (n=8), low DEHP group (n=9), and high DEHP group(n=7). DEHP[100 or 500 mg/(kg·d)], DES[100 μg/(kg·d)] and corn oil were administrated respectively to the pregnant mice from gestation day 12(GD 12) until postnatal day 3(PND3). The incidence of cryptorchidism with testicular morphologic and histological changes in the male pups was observed.Results: Significantly increased incidence of cryptorchidism was seen in the male pups with increasing exposure to DEHP. Cryptorchid testicular volumes and weights significantly decreased compared with the control. Abnormal pathological and ultrastructural alternations of seminiferous epithelium and Leydig cells were also observed. Meanwhile less or no sperm was found in the lumen of the epididymis.Conclusion: During the critical period of male sexual differentiation, exposure to DEHP may lead to a significantly high incidence of cryptorchidism, testicular damage and fertility impairment in the male offspring. The effects of DEHP are dosage-dependent.