Maternal exposure to a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppressed the development of reproductive organs of male rats: Dose-dependent increase of mRNA levels of 5 alpha-reductase type 2 in contrast to decrease of androgen receptor in the pubertal ventral prostate

To assess the health risks associated with exposure to 2,3,7,8-tetrachlorod ebenzo-p-dioxin (TCDD), we studied the effects of a relatively low dose of TCDD on the male reproductive system of rats, using the experimental protoc ol of T. A. Mably et al. (1992, Toxicol. Appl. Pharmacol. 114, 97-107, 108- 117, 118-126), and searched for the most sensitive and reliable among sever al indices of TCDD toxicity. Pregnant Holtzman rats were given a single ora l dose of 0, 12.5, 50, 200, or 800 ng TCDD/kg body weight on gestational da y (GD) 15, and male offspring were sacrificed on postnatal day (PND) 49 or 120. GC-MS analysis of the abdominal fat tissue and testis clearly showed i ncreased amounts of TCDD in these offspring. However, there was no TCDD eff ect on body weight of offspring. There were no changes on testicular or epi didymal weights by TCDD administration, even at the 800-ng/kg dose in rats sacrificed on either PND 49 or 120. In addition, TCDD administration result ed in no changes in daily sperm production or sperm reserve at any of the d oses used. However, the weight of the urogenital complex, including the ven tral prostate, was significantly reduced at doses of 200 and 800 ng TCDD/kg in rats sacrificed on PND 120. Moreover, the anogenital distance (AGD) of male rats sacrificed on PND 120 showed a significant decrease in the groups receiving doses greater than 50 ng TCDD/kg. TCDD administration resulted i n no apparent dose-dependent changes in levels of either serum testosterone or luteinizing hormone. Interestingly, reverse transcription-polymerase ch ain reaction (RT-PCR) analysis revealed that, in the ventral prostates of t he PND 49 group, TCDD administration resulted in both a dose-dependent incr ease in Sa-reductase type 2 (5 alphaR-II) mRNA level and a dose-dependent d ecrease in androgen receptor (AR) mRNA level. These results suggest that lo w-dose TCDD administration had a greater effect on the development of the e xternal genital organs and ventral prostate than on development of the test is and other internal genital organs. Moreover, it is highly suggested that the decrease in the size of the ventral prostate by maternal TCDD exposure might be due to decreased responsiveness of the prostate to androgen due t o an insufficient expression level of androgen receptor during puberty.