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

Abstract

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.

Gene-environment interaction and male reproductive function

“…Following exposure to TCDD in adult life, strains with a mutated AHR allele had a less pronounced decrease in spermatogenesis than those with the wild-type receptor [21]. Similarly, when exposed to the same compound in utero, males of the rat strains carrying the mutated allele had a lower decrease in daily sperm production and epididymal sperm reserves than counterparts with the wild-type allele when measured on postnatal day 70 [22]. Thus, the effects of TCDD exposure on spermatogenesis seemed to be decreased in rats with a mutated AHR, implying that a fully functioning receptor is needed for maximal negative exposure effects on spermatogenesis.…”

“…Thus, the effects of TCDD exposure on spermatogenesis seemed to be decreased in rats with a mutated AHR, implying that a fully functioning receptor is needed for maximal negative exposure effects on spermatogenesis. Although it is not fully explained how a mutated AHR can protect against the deleterious effects of dioxin on sperm number, the paper by Simanainen et al [22] showed that the effect is not mediated through reduction in testosterone production or poor development of seminal vesicles.…”

Risks and Management of Dioxins and Dioxin-like Compounds in Baltic Sea Fish: An Integrated Assessment

“…Among rats, differences between strains are seen due e.g. to aberrant AhR in TCDD-resistant strains (Simanainen et al 2004). Also salmonid strains differ greatly in their susceptibility to DLCs (Hornung et al 1996a), due e.g.…”

“…2002;10 Hendriks &Enserink 1996, based on levels in 1950's-70's (extrapolated from CB 153 andΣPCBs) Powell & al. 1997a for double-crested cormorant; 12 13 Based on mean TEq values for the main diet species sprat in GF ) and BP 14 Storr- 15 ; WHO-TEqs for fish have been used; 16 Hario & al. 2004, conversion 19 Powell & al.…”

Possible involvement of arylhydrocarbon receptor variants in TCDD-induced thymic atrophy and XRE-dependent transcriptional activity in Wistar Hannover GALAS rats

“…Although WH rats have been extensively used in the risk assessment of various chemicals, a substrain of WH rats, named Han/Wistar (Kuopio), has toxicities caused by dioxins (Pohjanvirta et al, 1993). In addition, between Long-Evans (L-E) and Han/Wistar (Kuopio) rat strains, there is a difference in susceptibiland reproductive disorders, depending on the different aryl hydrocarbon receptor (AhR) sequence (Pohjanvirta and Tuomisto, 1994;Viluksela et al, 2000;Simanainen et al, 2002Simanainen et al, , 2004. However, it is not known whether there is a difference in the transactivation activity depending on the AhR sequence among rat strains.…”