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9 December 2009 Comparative Contribution of the Aryl Hydrocarbon Receptor Gene to Perinatal Stage Development and Dioxin-Induced Toxicity Between the Urogenital Complex and Testis in the Mouse
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Abstract

TCDD (2,3,7,8-tetrachlorodebenzo-p-dioxin) requires the presence of the aryl hydrocarbon receptor (Ahr) gene for its toxic effects, such as reproductive disorders in male offspring of maternally exposed rats and mice. To study the involvement of the Ahr gene in producing the toxic phenotype with respect to testicular development, we administered a relatively high dose of TCDD to mice with three different maternally derived Ahr genotypic traits, and then compared several Ahr-dependent alterations among male reproductive systems on Postnatal Day 14. Reduction in anogenital distance and expression of prostatic epithelial genes in the urogenital complex (UGC) were detected in Ahr / and Ahr /− mice exposed to TCDD, whereas no difference was observed in Ahr−/− mice. In situ hybridization revealed the absence of probasin mRNA expression in the prostate epithelium, despite the obvious development of prostatic lobes in TCDD-exposed mice. In contrast to obvious prostatic dysfunction and induction of cytochrome P450 (CYP) family genes in the UGC by TCDD, no alterations in testicular functions were observed in germ cell/Sertoli cell/interstitial cell marker gene expression or CYP family induction. No histopathological changes were observed among the three genotypes and between control and TCDD-exposed mice. Therefore, mouse external genitalia and prostatic development are much more sensitive to TCDD treatment than testis. Further, the Ahr gene, analyzed in this study, does not significantly contribute to testicular function during perinatal and immature stages, and the developing mouse testis appears to be quite resistant to TCDD exposure.

Seiichiroh Ohsako, Noriho Fukuzawa, Ryuta Ishimura, Takashige Kawakami, Qing Wu, Reiko Nagano, Hiroko Zaha, Hideko Sone, Junzo Yonemoto, and Chiharu Tohyama "Comparative Contribution of the Aryl Hydrocarbon Receptor Gene to Perinatal Stage Development and Dioxin-Induced Toxicity Between the Urogenital Complex and Testis in the Mouse," Biology of Reproduction 82(3), 636-643, (9 December 2009). https://doi.org/10.1095/biolreprod.109.080812
Received: 13 August 2009; Accepted: 1 November 2009; Published: 9 December 2009
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