Therefore, the resistance alleles appear to selectively modify the TCDD effects on the adult male reproductive system. For type II endpoints e. Because of different sensitivities of the rat lines, the TCDD doses were between 0. The type I endpoints increased EROD activity, decreased thymus weight, and tooth defect are independent of genotype variation, and the rat lines respond similarly to TCDD exposure. The lower maximal doses in line B and line C rats compared to the doses in line A rats were chosen to keep the doses below the respective LD50 values of each rat line. The TCDD was weighed and dissolved in diethyl ether. In the previous study with line A, B, and C rats, we demonstrated that the male reproductive organ defects after in utero and lactational TCDD exposure were not profoundly affected by the resistance alleles.
The type I endpoints increased EROD activity, decreased thymus weight, and tooth defect are independent of genotype variation, and the rat lines respond similarly to TCDD exposure. Dosing solutions were mixed in a magnetic stirrer and sonicated for 20 min before dosing. Line A, B, and C rats were randomly divided into experimental groups of 5—6 5. The C-terminus of AHR is required for the formation of functional AHR conformation, which increases promoter accessibility and facilitates promoter occupancy by different transcription factors Ko et al. For type II endpoints e. The TCDD was weighed and dissolved in diethyl ether. The dose-responses of TCDD effects on male reproductive organ weights, sperm numbers, and serum testosterone concentrations were analyzed 17 days after exposure. Male reproductive toxicity is one of the most sensitive and extensively studied toxic endpoints of TCDD that is considered to belong to a group of environmental endocrine disrupters. The crossing protocol to develop these lines has been described earlier Tuomisto et al. Therefore, the resistance alleles appear to selectively modify the TCDD effects on the adult male reproductive system. Male rats were 12—16 weeks old at the beginning of the experiment. The rats were housed in stainless steel wire-bottom cages, 1—3 rats per cage, and given commercial rat chow R36; Lactamin, Stockholm, Sweden and tap water ad libitum. Line C rats do not have resistance alleles. Because the promoter sequences and the transcription factor machinery vary among genes, it could be hypothesized that the mutation in the Ahrhw selectively affects the formation of functional AHR conformation as well as communication between enhancer and promoter, leading to altered expression of different genes. Control animals were dosed similarly with corn oil vehicle. Because of different sensitivities of the rat lines, the TCDD doses were between 0. The lower maximal doses in line B and line C rats compared to the doses in line A rats were chosen to keep the doses below the respective LD50 values of each rat line. Thus the effect was observed only in resistant lines A and B. In the present study we analyzed the effects of adult TCDD exposure on the structure and function of male reproductive organs. Advanced Search Abstract 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: The dosing groups and the number of animals per dosing group are presented in Table 1. Our recent dose-response analysis showed that the typical endpoints of dioxin short-term toxicity can be classified on the basis of efficacy modification by the resistance alleles Ahrhw and Bhw Simanainen et al. However, the decrease in daily sperm production and cauda epididymal sperm number was reduced by the resistance alleles Simanainen et al. Adjusted volume of diethyl ether was mixed with corn oil and ether was let to evaporate. The rats were kept under a photoperiodic cycle of 12 h light per 12 h dark in an air-conditioned animal room. Significant decrease in spermatogenesis was observed in each rat line, but the amount of decrease was reduced by resistance alleles.
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