title: Distribution of 14C-2,3,7,8-tetrachlorodibenzo-p-dioxin to the brain and peripheral tissues of fetal rats and its comparison with adults.
abstract: Some forms of reproductive and developmental toxicity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) occur via initial damage to the pituitary synthesis of gonadotropins followed by the reduced expression of gonadal steroidogenic proteins. Defects in gonadotropin synthesis are highly specific to the periods from late fetal to early newborn stages. The reason for this specificity remains unknown. To address this issue, we compared the tissue distribution of 14C-TCDD between fetal and adult rats. In adult male rats, the major portion of TCDD given orally (approximately 33-42% dose) accumulated in the liver during day 1 and 5 after treatment. Very little TCDD (approximately 0.01% of the dose) distributed into the brain. A similar picture was also observed in TCDD-treated pregnant rats. The amount of TCDD transferred from a dam to the fetuses was extremely low (around 0.02% of the maternal dose/fetus) after 1 day of treatment. Male and female fetuses showed the same pattern in the brain distribution of TCDD. The rate of TCDD distribution to fetal brain, which was calculated on the basis of body burden to a fetus, was 100 times or more than that in adults. However, the brain content of TCDD (ng/g tissue) was comparable in fetuses and their dams, and adult males exposed to TCDD. These results suggest that although TCDD easily translocates to fetal brain, this is not a major mechanism for a fetal age-specific reduction in gonadotropin synthesis.
authors.forename: Takumi
authors.initials: T
authors.lastname: Ishida
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Tomoki
authors.initials: T
authors.lastname: Takeda
authors.forename: Takayuki
authors.initials: T
authors.lastname: Koga
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishii
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamada
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure; D000072317:Polychlorinated Dibenzodioxins / Q000493:pharmacokinetics*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D000072317:Polychlorinated Dibenzodioxins