Li He-Cheng, Chen Qi, Wang Zi-Ming, Gan Wei-Min, Cheng Wei, Chong Tie, Shi Tao, Qiu Shu-Dong, Ge Ling, Wang Xin-Yang
Department of Urology, 2nd Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710004, China.
Zhonghua Nan Ke Xue. 2008 Feb;14(2):142-8.
To investigate the effects of prepubertal exposure to diethylstilbestrol (DES) on the testicular development and function of Sprague-Dawley (SD) rats.
Ninety 21-day-old male SD rats were randomly and equally divided into 4 experimental groups (Da, Db, Dc and Dd), which were injected with DES dissolved in corn oil at the dose of 0.01, 0.1, 1.0 and 10.0 microg/(kg x d) from postnatal day (PND) 22 to 35, and a control group (C), which received vehicle only. The testicular development of all the rats was observed, and their testes were harvested in the stages of late puberty (PND 50), sexual maturity (PND 64) and adulthood (PND 130) respectively to determine the weight and histological features of the testis and examine the quality of the sperm in the epididymal cauda of the PND 130 rats.
The testis descent in the C, Da, Db, Dc and Dd groups occurred on PND 26.17 +/- 1.94, 26.83 +/- 1.47, 28.68 +/- 1.03, 33.50 +/- 1.87 and 41.50 +/- 2.74 respectively, significantly delayed in the Db, Dc and Dd groups compared with the C group (P < 0.05 or P < 0.01). On PND 50, the unilateral testis weights in the C, Da, Db, Dc and Dd groups were (1.38 +/- 0.01) g, (1.38 +/- 0.12) g, (1.30 +/- 0.14) g, (0.86 +/- 0.18) g and (0.73 +/- 0.27) g respectively, significantly less in the Dc and Dd groups than in the C group (P < 0.01). Compared with the C group, there was a slight decrease in the number of the cells in the epithelia of a few seminiferous tubules in the Db group on PND 50, maldevelopment of seminiferous tubules, reduced cell number in seminiferous epithelia, blocked spermatogenesis and aplasia of Leydig cells in the Dc and Dd groups in a dose-dependent manner. On PND 64, the unilateral testis weights in the C, Da, Db, Dc and Dd groups were (1.60 +/- 0. 06) g, (1.62 +/- 0.11) g, (1.58 +/- 0.08) g, (1.47 +/- 0.10) g and (0.99 +/- 0.37) g respectively, significantly less in the Dc and Dd groups than in the C group (P < 0.05 or P < 0.01), and the histological alteration of the testis in the Dc and Dd groups was similar to or less than that on PND 50. On PND 130, no statistic difference was observed either in unilateral testis weight or in the histological features of the testis between any experimental group and the control (P > 0.05). The sperm concentration in the epididymal cauda in the C, Da, Db, Dc and Dd groups were (73.00 +/- 16.90) x 10(6)/ml, (68.00 +/- 19.67) x 10(6)/ml, (68.67 +/- 12.15) x 10(6)/ml, (35.17 +/- 15.64) x 10(6)/ml and (19.13 +/- 5.17) x 10(6)/ml, significantly lower in the Dc and Dd groups than in the C group (P < 0.01). There was a significant decrease in sperm motility in the Dd group (P < 0.01), the percentage of grade a sperm in the Db, Dc and Dd groups (P < 0.05) and the percentage of grade b sperm in the Dd group (P < 0.01).
Prepubertal exposure to low dose of DES (0.01 microg/[kg x d] x 14 d) does not significantly affect the testicular development and function of SD rats, while high dose (1.0-10.0 microg/[kg x d] x 14 d) has significant short- (PND 50 and 64) or long-term (PND 130) toxic effect, which increases with dose and decreases with age. The mechanism of the toxic effect involves the insults to the development and function of Leydig and Sertoli cells.
探讨青春期前暴露于己烯雌酚（DES）对斯普拉格-道利（SD）大鼠睾丸发育及功能的影响。
将90只21日龄雄性SD大鼠随机等分为4个实验组（Da、Db、Dc和Dd），从出生后第22天（PND）至35天，分别按0.01、0.1、1.0和10.0μg/（kg·d）的剂量腹腔注射溶于玉米油的DES，另设一个对照组（C），仅给予溶媒。观察所有大鼠的睾丸发育情况，并分别在青春期后期（PND 50）、性成熟期（PND 64）和成年期（PND 130）收取睾丸，测定睾丸重量和组织学特征，并检查PND 130大鼠附睾尾精子质量。
C、Da、Db、Dc和Dd组睾丸下降分别发生在PND 26.17±1.94、26.83±1.47、28.68±1.03、33.50±1.87和41.50±2.74，与C组相比，Db、Dc和Dd组显著延迟（P<0.05或P<0.01）。在PND 50时，C、Da、Db、Dc和Dd组单侧睾丸重量分别为（1.38±0.01）g、（1.38±0.12）g、（1.30±0.14）g、（0.86±0.18）g和（0.73±0.27）g，Dc和Dd组显著低于C组（P<0.01）。与C组相比，PND 50时Db组少数生精小管上皮细胞数量略有减少，Dc和Dd组生精小管发育不良、生精上皮细胞数量减少、精子发生受阻及Leydig细胞发育不全，且呈剂量依赖性。在PND 64时，C、Da、Db、Dc和Dd组单侧睾丸重量分别为（1.60±0.06）g、（1.62±0.11）g、（1.58±0.08）g、（1.47±0.10）g和（0.99±0.37）g，Dc和Dd组显著低于C组（P<0.05或P<0.01），且Dc和Dd组睾丸组织学改变与PND 50时相似或减轻。在PND 130时，各实验组与对照组相比，单侧睾丸重量及睾丸组织学特征均无统计学差异（P>0.05）。C、Da、Db、Dc和Dd组附睾尾精子浓度分别为（73.00±16.90）×10⁶/ml、（68.00±19.67）×10⁶/ml、（68.67±12.15）×10⁶/ml、（35.17±15.64）×10⁶/ml和（19.13±5.17）×10⁶/ml，Dc和Dd组显著低于C组（P<0.01）。Dd组精子活力显著降低（P<0.01），Db、Dc和Dd组a级精子百分比（P<0.05）及Dd组b级精子百分比（P<0.01）均显著降低。
青春期前暴露于低剂量DES（0.01μg/[kg·d]×14 d）对SD大鼠睾丸发育及功能无显著影响，而高剂量（1.0～10.0μg/[kg·d]×14 d）具有显著的短期（PND 50和64）或长期（PND 130）毒性作用，且随剂量增加而增强，随年龄增长而减弱。毒性作用机制涉及对Leydig细胞和支持细胞发育及功能的损害。
