Distribution of 14C-2,3,7,8-tetrachlorodibenzo-p-dioxin to the brain and peripheral tissues of fetal rats and its comparison with adults
Distribution of 14C-2,3,7,8-tetrachlorodibenzo-p-dioxin to the brain and peripheral tissues of fetal rats and its comparison with adults
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DOI：
10.2131/jts.35.563
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发表时间：
2010-08-01
影响因子：
2
通讯作者：
Yamada, Hideyuki
中科院分区：
文献类型：
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作者：
Ishida, Takumi;Matsumoto, Yuki;Yamada, Hideyuki
2,3,7,8-四氯二苯并-对-二恶英 (TCDD) 的某些形式的生殖和发育毒性是通过最初损害垂体促性腺激素合成，随后导致性腺类固醇生成蛋白表达减少而发生的。促性腺激素合成缺陷在胎儿晚期到新生儿早期阶段具有高度特异性。这种特殊性的原因仍然未知。为了解决这个问题，我们比较了胎儿和成年大鼠之间 C-14-TCDD 的组织分布。在成年雄性大鼠中，口服给药的 TCDD 的主要部分（约 33-42% 剂量）在治疗后第 1 天和第 5 天积聚在肝脏中。很少的 TCDD（大约剂量的 0.01%）分布到大脑中。在 TCDD 治疗的怀孕大鼠中也观察到类似的情况。治疗 1 天后，从母鼠转移到胎儿的 TCDD 量极低（约为母体剂量/胎儿的 0.02%）。男性和女性胎儿的 TCDD 大脑分布表现出相同的模式。根据对胎儿的身体负担计算，TCDD在胎儿大脑中的分布率是成人的100倍甚至更多。然而，胎儿及其母鼠以及暴露于 TCDD 的成年男性的脑中 TCDD 含量（ng/g 组织）相当。这些结果表明，虽然 TCDD 很容易转移到胎儿大脑，但这并不是胎儿年龄特异性促性腺激素合成减少的主要机制。
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 C-14-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.