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ToxSci Advance Access published online on July 7, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh212
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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Received April 7, 2004
Accepted June 26, 2004

Reproductive and Developmental Toxicology

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

Ulla Simanainen 1*, Annika Adamsson 2, Jouni T. Tuomisto 3, Hanna M. Miettinen 3, Jorma Toppari 4, Jouko Tuomisto 1, Matti Viluksela 3

1 National Public Health Institute, Department of Environmental Health, P.O. Box 95, FIN-70701 Kuopio, Finland; University of Kuopio, P.O. Box 1687, FIN-70701 Kuopio, Finland
2 Department of Biology, Laboratory of Animal Physiology, University of Turku, FIN-20014 Turku, Finland
3 National Public Health Institute, Department of Environmental Health, P.O. Box 95, FIN-70701 Kuopio, Finland
4 Department of Physiology, University of Turku, FIN-20520 Turku, Finland; Department of Pediatrics, University of Turku, FIN-20520 Turku, Finland

* To whom correspondence should be addressed. E-mail: ulla.simanainen{at}ktl.fi.


  Abstract

Contribution of genetic factors to adult male reproductive system toxicity of 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 or above. Thus the effect was only observed 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. Thus, the resistance alleles appear to selectively modify the TCDD effects on 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.

Keywords: dioxin; TCDD; strain differences; adult exposure; male reproductive toxicity.
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