环境内分泌干扰因子DEHP与隐睾发病相关性的实验研究

目的　探讨邻苯二甲酸二异辛酯 (DEHP)诱导KM小鼠隐睾发生的作用及致病机制。方法　以己烯雌酚 (Diethylstilbestrol,DES)为阳性对照 ,孕鼠在妊娠期第 12d至分娩后第 3d每日灌胃给药DEHP ,分为低剂量组、高剂量组 ,观察雄性仔鼠隐睾发生情况及睾丸形态、组织学改变 ;应用免疫组织化学方法检测睾丸雌激素受体和雄激素受体的表达水平 ,应用放射免疫测定法测定仔鼠血清睾酮、雌二醇、卵泡刺激素和黄体生成素水平。结果　随给药剂量的增大 ,孕鼠未出现明显毒性反应 ,而雄性仔鼠隐睾发生率明显增高 ;隐睾鼠的睾丸、附睾重量及睾丸体积较非隐睾鼠明显降低 ,光镜和电镜下隐睾曲细精管上皮和间质细胞均出现明显异常和超微结构改变 ;同时雄性仔鼠血清睾酮、黄体生成素水平降低 ,卵泡刺激素水平增高 ,雌激素受体表达水平降低。结论　在雄性小鼠性分化的关键时期 ,DEHP可导致其隐睾发生 ,其发生率与剂量存在一定的相关性 ,其作用机制尚需进一步研究。

Experimental study on the relationship between environmental endocrine disruptor DEHP and cryptorchidism in mice

Objective To investigate the effects of Di-(2-ethylhexyl) phthalate (DEHP) on the incidence of cryptorchidism in mice.Methods Different dosages of DEHP were administered to adult mice from the 14th day of gestation to the third day after delivery. The incidence of cryptorchidism and testicular morphological and histological alterations in male pups were observed. Immunohistochemical staining was employed to determine the expression of androgen receptor (AR) and estrogen receptor (ER) in testes. Plasma testosterone (T), estradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH) in male offspring were measured through radioimmunoassay.Results There were no significant toxic effects on dams with higher dosage administration of DEHP. The incidence of cryptorchidism in male pups, however, was significantly elevated when the mothers got higher dosage of DEHP. Compared to the control group, the weight and volume of cryptorchid testes were significantly decreased in experimental group. And the abnormal pathological and ultrastructural alterations of seminiferous epithelium and Leydig cells were also noted in cryptorchidism group. Moreover, the ER expression in testes was decreased in this group. Compared to the control group, plasma levels of T and LH were decreased while FSH levels were elevated in experimental group.Conclusions During the critical period of male sexual differentiation, exposure to DEHP may increase the incidence of cryptorchidism and testicular damages in male offsprings.