Lindström P, Harris M, Ross M, Lamb J C, Chapin R E
National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Fundam Appl Toxicol. 1988 Oct;11(3):528-39. doi: 10.1016/0272-0590(88)90117-0.
Androgen binding protein (ABP), produced by Sertoli cells and released into seminiferous tubules and blood, was measured in the serum of di-n-pentyl phthalate (DPP)-treated rats as a potential index of germinal epithelial damage. A single oral dose of DPP (0, 0.25, 1.0, or 2.0 g/kg body wt in corn oil) was given to four groups of 110 Fischer 344 rats; 10 rats per group were killed weekly for 10 weeks. Effects of treatment on serum ABP were then compared with effects on other reproductive endpoints. Treatment did not produce any significant effect on body weight or weights of liver, kidney, prostate, and seminal vesicles. In high-dose rats, serum ABP values more than doubled 2 days after injection, remained significantly elevated for 3 weeks, then fell and remained significantly below control values from Week 4 through Week 10. Accordingly, 95% of the rats in this group showed greater than 50% of the seminiferous tubules degenerated, decreased epididymal sperm density, reduced testicular and epididymal weights, and up to 97% morphologically abnormal sperm. In medium-dose rats, serum ABP increased up to 48% during the first week, returned to control values by Week 2, and remained at control levels thereafter. Of these rats, 20% showed 20-50% degenerated tubules, decreased sperm density, reduced testicular and epididymal weights (which were not always statistically significant), and up to 23% abnormal sperm morphology. In low-dose rats, serum ABP levels were similar to those of controls, and the other parameters, except sperm density, also remained unchanged. To examine the effects of DPP on fertility, a second group of rats was exposed in an identical manner [gavaged once with DPP in corn oil (0, 0.25, 1.0, and 2.0 g/kg body wt)], then mated to untreated females at 3, 6, and 10 weeks postexposure. DPP at 2 (but not 1.0 or 0.25) g/kg caused a significant reduction in pregnancies and live pups and a significant increase in preimplantation loss. Histopathology of the testis in the first experiment suggested a very slow recovery. Therefore, controls and high-dose rats in the mating trial were killed 14, 18, and 30 weeks after dosing and the germinal epithelium was evaluated histologically. All high-dose animals showed testicular lesions typical of phthalate ester exposure and the epithelium did not recover within 30 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)
雄激素结合蛋白（ABP）由支持细胞产生并释放到生精小管和血液中，在邻苯二甲酸二正戊酯（DPP）处理的大鼠血清中进行检测，作为生精上皮损伤的潜在指标。将四组110只Fischer 344大鼠分别经口给予单次剂量的DPP（0、0.25、1.0或2.0 g/kg体重，溶于玉米油中）；每组每周处死10只大鼠，共持续10周。然后将处理对血清ABP的影响与对其他生殖终点的影响进行比较。处理对体重以及肝脏、肾脏、前列腺和精囊的重量均未产生任何显著影响。在高剂量组大鼠中，注射后2天血清ABP值增加了一倍多，在3周内一直显著升高，然后下降，从第4周一直到第10周都显著低于对照值。相应地，该组95%的大鼠显示超过50%的生精小管退化，附睾精子密度降低，睾丸和附睾重量减轻，高达97%的精子形态异常。在中剂量组大鼠中，血清ABP在第一周内最多增加48%，到第2周恢复到对照值，此后一直维持在对照水平。在这些大鼠中，20%显示20 - 50%的小管退化，精子密度降低，睾丸和附睾重量减轻（并非总是具有统计学意义），高达23%的精子形态异常。在低剂量组大鼠中，血清ABP水平与对照组相似，除精子密度外的其他参数也保持不变。为了研究DPP对生育力的影响，另一组大鼠以相同方式暴露[经口给予一次溶于玉米油中的DPP（0、0.25、1.0和2.0 g/kg体重）]，然后在暴露后3、6和10周与未处理的雌性交配。2 g/kg（但不是1.0或0.25 g/kg）的DPP导致怀孕和活仔数显著减少，着床前损失显著增加。第一个实验中睾丸的组织病理学表明恢复非常缓慢。因此，在交配试验中的对照组和高剂量组大鼠在给药后14、18和30周处死，并对生精上皮进行组织学评估。所有高剂量动物均表现出典型的邻苯二甲酸酯暴露引起的睾丸损伤，且上皮在30周内未恢复。（摘要截断于400字）
