Wilker C, Johnson L, Safe S
Department of Veterinary Anatomy and Public Health, Texas A&M University, College Station 77843-4466, USA.
Toxicol Appl Pharmacol. 1996 Nov;141(1):68-75. doi: 10.1006/taap.1996.0261.
Treatment of pregnant female Sprague-Dawley rats on Gestational Day 15 with a single oral dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.5, 1.0, or 2.0 micrograms/kg) or indole-3-carbinol (I3C, 1.0 or 100 mg/kg), an aryl hydrocarbon (Ah) receptor agonist which is found in cruciferous vegetables, resulted in reproductive abnormalities in the male offspring (three to five litters in each treatment group). Anogenital distance and crown to rump length were altered by both compounds; however, the timing of the effects (Day 1 or 5) was variable and the responses were not necessarily dose-dependent. In 62-day-old offspring, seminal vesicle (24 to 26%), prostate (32 to 44%), testicular parenchymal (14%), and epididymal weight (19%) were decreased by one or more doses of TCDD. In contrast, I3C at one or more doses decreased daily sperm production/g testicular parenchyma (13 to 20%) and daily sperm production/testis (22%). Total number of sperum in the epididymis was significantly decreased (30 to 33%) in rats perinatally exposed to TCDD and this was due to a decreased (49 to 51%) number of sperm in the tail of the epididymis. Perinatal exposure to I3C did not affect any of these parameters. TCDD did not affect epididymal transit time of sperm through the complete epididymis at any of the doses (0.5 to 2.0 micrograms/kg). However, at the two highest doses (1.0 and 2.0 micrograms/kg), TCDD increased epididymal transit rate of sperm through the tail of the epididymis by 33 and 37%, respectively. In contrast, primarily due to decreased transit rate (39%) of sperm through the head plus body of the epididymis. I3C (1 mg/kg) significantly increased total epididymal transit time by 31%. In conclusion, perinatal exposure of pregnant rats to I3C, an Ah receptor agonist similar to TCDD, causes reproductive abnormalities in male rat offspring; however, I3C and TCDD elicited both common and different responses.
在妊娠第15天,给雌性斯普拉格-道利大鼠单次口服剂量的2,3,7,8-四氯二苯并-对-二恶英(TCDD)(0.5、1.0或2.0微克/千克)或吲哚-3-甲醇(I3C,1.0或100毫克/千克,一种存在于十字花科蔬菜中的芳烃(Ah)受体激动剂),导致雄性后代出现生殖异常(每个治疗组有三到五窝)。两种化合物均改变了肛门生殖器距离和冠臀长度;然而,效应出现的时间(第1天或第5天)是可变的,且反应不一定呈剂量依赖性。在62日龄的后代中,一个或多个剂量的TCDD使精囊(24%至26%)、前列腺(32%至44%)、睾丸实质(14%)和附睾重量(19%)降低。相比之下,一个或多个剂量的I3C使每克睾丸实质的每日精子生成量(13%至20%)和每日睾丸精子生成量(22%)降低。围产期暴露于TCDD的大鼠附睾中的精子总数显著减少(30%至33%),这是由于附睾尾部精子数量减少(49%至51%)。围产期暴露于I3C对这些参数均无影响。TCDD在任何剂量(0.5至2.0微克/千克)下均不影响精子通过整个附睾的转运时间。然而,在两个最高剂量(1.0和2.0微克/千克)下,TCDD使精子通过附睾尾部的转运速率分别提高了33%和37%。相比之下,主要是由于精子通过附睾头部加体部的转运速率降低(39%)。I3C(1毫克/千克)使附睾总转运时间显著增加了31%。总之,妊娠大鼠围产期暴露于与TCDD类似的Ah受体激动剂I3C会导致雄性大鼠后代出现生殖异常;然而,I3C和TCDD引发了共同和不同的反应。