Adult 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) Exposure and Effects on Male Reproductive Organs in Three Differentially TCDD-Susceptible Rat Lines

The contribution of genetic factors to adult male reproductive system toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was analyzed in three rat lines differentially resistant to TCDD acute lethality: line A, B, and C rats (selectively bred from TCDD-resistant Han/Wistar [Kuopio; H/W] and TCDD-sensitive Long-Evans [Turku/AB; L-E] rats). The resistance is linked to a mutated H/W-type aryl hydrocarbon receptor allele in line A and to an H/W-type unknown “B” allele in line B. Line C rats do not have resistance alleles. Mature male line A, B and C rats were given single oral doses up to 1000, 300, and 30 μg/kg TCDD, respectively. The dose-responses of TCDD effects on male reproductive organ weights, sperm numbers, and serum testosterone concentrations were analyzed 17 days after exposure. Serum testosterone concentrations were decreased by the highest doses of TCDD, and there were no major sensitivity differences among the rat lines. Correspondingly, the decrease in relative weight of ventral prostate and seminal vesicles was seen only after a dose of ≥100 μg/kg TCDD. Thus the effect was observed only in resistant lines A and B. The relative weights of testes and epididymides were not affected. Significant decrease in spermatogenesis was observed in each rat line, but the amount of decrease was reduced by resistance alleles. The highest TCDD dose decreased the daily sperm production by 37, 38, and 60% in line A, B, and C rats, respectively. Therefore, the resistance alleles appear to selectively modify the TCDD effects on the adult male reproductive system. The fact that the influence of resistance alleles on spermatogenesis is different from that on androgenic status indicates that the effect of TCDD on sperm numbers is not fully related to decreased serum testosterone.