Pattern of Male Reproductive System Effects After in Utero and Lactational 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Exposure in Three Differentially TCDD-Sensitive Rat Lines.

摘要

Male reproductive effects induced by in utero and lactational exposure to TCDD were analyzed in three rat lines that are differently sensitive to TCDD. Rats from lines A, B, and C were selectively bred from TCDD-resistant Han/Wistar (Kuopio, H/W) and TCDD-sensitive Long-Evans (Turku/AB, L-E) rats and exhibited very different LD50 values for TCDD: >10,000, 830, and 40 microg/kg in males, respectively. The resistance in line A rats was linked to a mutated H/W-type aryl hydrocarbon receptor (Ahr(hw)) and in line B rats to a H/W-type unknown allele B (B(hw)). Line C rats had no resistance alleles. Influence of the resistance alleles on developmentally induced male reproductive effects of TCDD was studied by exposing pregnant females to TCDD (0.03, 0.1, 0.3, or 1 microg/kg) on gestation day (GD) 15. Male progeny were sacrificed on postnatal day (PND) 70. Next, the dams were given 1 microg/kg TCDD on GD 15 and male progeny were sacrificed on PND 14, 21, 28, 35, or 49. Serum testosterone concentration, male sex organ weights, and testicular and cauda epididymal sperm numbers were analyzed; the most sensitive end point was decreased sperm numbers. The dose of 1 microg/kg TCDD reduced daily sperm production by 9.3, 25, and 36%, and cauda epididymal sperm reserves by 18, 42, and 49% in rat lines A, B, and C when measured on PND 70, respectively. The most consistent and significant effect was decreased weight of prostate lobes. The growth of the male reproductive organs was not markedly affected by the resistance alleles Ahr(hw) and B(hw). In contrast, the effects on sperm parameters appeared to be slightly modified by the resistance alleles. Thus, the intraspecies genetic differences in C-terminal transactivation domain of AHR appear to modify the sensitivity to only certain dioxin-induced male reproductive effects.