Bell David R, Clode Sally, Fan Ming Qi, Fernandes Alwyn, Foster Paul M D, Jiang Tao, Loizou George, MacNicoll Alan, Miller Brian G, Rose Martin, Tran Lang, White Shaun
School of Biology, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
Toxicol Sci. 2007 Sep;99(1):224-33. doi: 10.1093/toxsci/kfm141. Epub 2007 Jun 1.
We have investigated whether fetal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes defects in the male reproductive system of the rat using chronically exposed rats to ensure continuous exposure of the fetus. Five- to six-week-old rats were exposed to control diet, or diet containing TCDD, to attain an average dose of 2.4, 8, and 46 ng TCDD/kg/day for 12 weeks, whereupon the rats were mated and allowed to litter; rats were switched to control diet after parturition. Male offsprings were allowed to develop until kills on PND70 (25 per group) or PND120 (all remaining animals). Offspring from the high-dose group showed an increase in total litter loss, and the number of animals alive on postnatal day (PND)4 in the high-dose group was approximately 26% less than control. The high and medium dose offsprings showed decreased weights at various ages. Balano-preputial separation (BPS) was significantly delayed in all three dose groups compared to control. There were no significant effects of maternal treatment when the offsprings were subjected to a functional observational battery or learning tests, with the exception that the high-dose group showed a deficit in motor activity. Twenty rats per group were mated to females, and there were no significant effects of maternal treatment on the fertility of these rats or on the F1 or F2 sex ratio. Sperm parameters at PND70 and 120 showed no significant effect of maternal treatment, with the exception that there was an increase in the proportion of abnormal sperm in the high-dose group at PND70; this is associated with the developmental delay in puberty in this dose group. There were no remarkable findings of maternal treatment on organ weights, with the exception that testis weights were reduced by approximately 10% at PND70 (but not PND120), and although the experiment was sufficiently powered to detect small changes, ventral prostate weight was not reduced. There were no significant effects of maternal treatment upon histopathological comparison of high-dose and control group organs. These data confirm that developmental exposure to TCDD shows no potent effect on adult sperm parameters or accessory sexual organs, but show that delay in BPS occurs after exposure to low doses of TCDD, and this is dependent upon whether TCDD is administered acutely or chronically.
我们使用长期暴露的大鼠来确保胎儿持续接触2,3,7,8-四氯二苯并对二恶英（TCDD），研究了胎儿接触TCDD是否会导致大鼠雄性生殖系统出现缺陷。将5至6周龄的大鼠喂食对照饮食或含TCDD的饮食，持续12周，平均剂量分别为2.4、8和46 ng TCDD/千克/天，之后让大鼠交配并产仔；产后大鼠改喂对照饮食。雄性后代饲养至PND70（每组25只）或PND120（所有剩余动物）后处死。高剂量组的总产仔损失增加，高剂量组出生后第4天（PND4）存活的动物数量比对照组少约26%。高剂量和中剂量组的后代在不同年龄段体重下降。与对照组相比，所有三个剂量组的阴茎包皮分离（BPS）均显著延迟。当对后代进行功能观察组合或学习测试时，母体处理没有显著影响，但高剂量组在运动活动方面存在缺陷。每组20只大鼠与雌性交配，母体处理对这些大鼠的生育能力或F1或F2性别比例没有显著影响。PND70和120时的精子参数显示母体处理没有显著影响，但高剂量组在PND70时异常精子比例增加；这与该剂量组青春期发育延迟有关。母体处理对器官重量没有显著影响，但睾丸重量在PND70时减少了约10%（PND120时未减少），尽管该实验有足够的能力检测微小变化，但腹侧前列腺重量没有减少。高剂量组和对照组器官的组织病理学比较显示母体处理没有显著影响。这些数据证实，发育过程中接触TCDD对成年精子参数或附属生殖器官没有显著影响，但表明低剂量TCDD暴露后会出现BPS延迟，这取决于TCDD是急性还是慢性给药。
