title: 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.
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.
authors.affiliation: Division of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ohsako@m.u-tokyo.ac.jp
authors.forename: Seiichiroh
authors.initials: S
authors.lastname: Ohsako
authors.forename: Noriho
authors.initials: N
authors.lastname: Fukuzawa
authors.forename: Ryuta
authors.initials: R
authors.lastname: Ishimura
authors.forename: Takashige
authors.initials: T
authors.lastname: Kawakami
authors.forename: Qing
authors.initials: Q
authors.lastname: Wu
authors.forename: Reiko
authors.initials: R
authors.lastname: Nagano
authors.forename: Hiroko
authors.initials: H
authors.lastname: Zaha
authors.forename: Hideko
authors.initials: H
authors.lastname: Sone
authors.forename: Junzo
authors.initials: J
authors.lastname: Yonemoto
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tohyama
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005260:Female; D047109:Fetal Development / Q000187:drug effects / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012098:Reproduction / Q000187:drug effects / Q000235:genetics; D013737:Testis / Q000187:drug effects / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism; D014566:Urogenital System / Q000187:drug effects / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism
chemical_list: D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon