青春期前邻苯二甲酸二丁酯持续暴露对大鼠睾丸发育的影响

Effects of Prepubertal Continuous Exposure to Dibutyl Phthalate on Testicular Development in Rats

目的:研究青春期前邻苯二甲酸二丁酯(DBP)持续暴露对睾丸发育的影响。方法:21日龄断乳青春期前雄性SD大鼠随机分为对照组(n=24)和实验组(n=54),每日分别用玉米油或DBP玉米油溶液灌胃,DBP暴露剂量分别为50mg/(kg.d)(低剂量组,n=18)、200mg/(kg.d)(中剂量组,n=18)和600mg/(kg.d)(高剂量组,n=18),各组动物持续暴露14、21、28d后(即PND35,PND42和PND49)断颈处死。记录大鼠体重变化,检测睾丸重量和体积、附属性器官重量及附睾精子,化学发光免疫分析法检测血清睾酮含量,苏木精-伊红染色观察睾丸组织形态学变化,测量生精小管平均直径及进行睾丸活检评分。结果:低剂量组PND35少量生精小管生精细胞排列紊乱,PND42和PND49睾丸、附属性器官发育及生精功能正常;中剂量组PND35和PND42生精细胞排列紊乱、数目减少,PND49生精小管内可见各级生精细胞及精子,睾丸未见萎缩,附属性器官发育正常;高剂量组大鼠体重增长减缓,血清睾酮水平低下,睾丸生精小管变性萎缩,生精上皮发育阻滞,生精细胞大量凋亡坏死,青春期大鼠睾丸萎缩,无精子,附睾、前列腺和精囊等附属性器官发育迟缓。结论:青春期前DBP持续暴露可损害睾丸组织发育和正常生精功能形成,其毒性效应具有剂量依赖性,高剂量DBP持续暴露引起的睾丸毒性在青春期前发育过程中不可修复,而低中剂量暴露引起的睾丸毒性在PND49之前可完全或部分逆转性恢复。

Objective： To investigate the effects of prepubertal continuous exposure to dibutyl phthalate （DBP） on the testis develop- ment in SD rats. Methods ： Twenty-one-day-old weanling prepubertal male SD rats were randomly divided into a control （ n = 24） and an experiment group （ n = 54）, garaged daily with corn oil vehicle or coin oil ＋ DBP at the repeated dose of 0 rag/（ kg · d） （ control）, 50 rag/（ kg · d） （low-dose）, 200 mg/（ kg · d） （medium-dose） and 600 mg/（ kg · d） （high-dose） for 14, 21 and 28 days, and then sacrificed by decapitation on PND35, PNIM2 and PND49. The body weight gain, the testis weight and volume and the weight of accessory sex organs were measured, the serum testosterone level assayed by chemoluminescence technique, the testis tissues stained by H＆E and observed under the light microscope for morphological alteration, the mean diameter of the seminiferous tubules determined and testicular biopsy scores obtained. Results ： Disordered arrangement of spermatogenic ceils was found in some seminiferous tubules on PND35 in the low-dose group, but testis development and spermatogenesis were normal on PND42 and PND49. In the medium-dose group, disordered arrangement and decreased number of spermatogenic cells were observed on PND35 and PND42, but without testicular atrophy, and various grades of spermatogenic cells and sperm were seen on PND49. High-dose DBP slowed down the body weight gain, decreased serum T levels and induced degeneration of seminiferous tubules, arrest of spermatogenic epithelium development and necrosis of spermatogenic cells. The pubertal rats （PND49） showed testicular atrophy, azoospermia and delayed development of accessory sex organs. Conclusion ： Prepubertal continuous exposure to DBP induces damages to testicular development and spermatogenesis in a dose-dependent manner, and those induced by high-dose DBP cannot be recuperated in the phase of prepubertal development, while the slight adverse effects on the testis induced by low- and medium-dose DBP could be completely or partly reversible before PND49.