Office of Research and Development, Centre for Public Health and Environmental Assessment, US Environmental Protection Agency, Research Triangle Park, North Carolina 27709, USA.
Office of Air Quality, US Environmental Protection Agency, Research Triangle Park, North Carolina 27709, USA.
Toxicol Sci. 2024 Feb 28;198(1):113-127. doi: 10.1093/toxsci/kfad133.
The environmental contaminant perchlorate impairs the synthesis of thyroid hormones by reducing iodine uptake into the thyroid gland. Despite this known action, moderate doses of perchlorate do not significantly alter serum thyroid hormone in rat pups born to exposed dams. We examined perchlorate dosimetry and responsivity of the thyroid gland and brain in offspring following maternal exposure to perchlorate. Pregnant rat dams were delivered perchlorate in drinking water (0, 30, 100, 300, 1000 ppm) from gestational day 6 to postnatal day (PN) 21. Perchlorate was present in the placenta, milk, and serum, the latter declining in pups over the course of lactation. Serum and brain thyroid hormone were reduced in pups at birth but recovered to control levels by PN2. Dramatic upregulation of Nis was observed in the thyroid gland of the exposed pup. Despite the return of serum thyroid hormone to control levels by PN2, expression of several TH-responsive genes was altered in the PN14 pup brain. Contextual fear learning was unimpaired in the adults, supporting previous reports. Declining levels of serum perchlorate and a profound upregulation of Nis gene expression in the thyroid gland are consistent with the rapid return to the euthyroid state in the neonate. However, despite this recovery, thyroid hormone insufficiencies in serum and brain beginning in utero and present at birth appear sufficient to alter TH action in the fetus and subsequent trajectory of brain development. Biomarkers of that altered trajectory remain in the brain of the neonate, demonstrating that perchlorate is not devoid of effects on the developing brain.
环境污染物高氯酸盐通过减少甲状腺对碘的摄取来破坏甲状腺激素的合成。尽管有这种已知的作用，但暴露于高氯酸盐的母鼠所生的幼鼠中，适量的高氯酸盐并不会显著改变血清甲状腺激素。我们研究了母体暴露于高氯酸盐后，幼鼠体内高氯酸盐的剂量学和甲状腺及大脑的反应性。从妊娠第 6 天到产后第 21 天，怀孕的大鼠母鼠通过饮用水（0、30、100、300、1000ppm）摄入高氯酸盐。高氯酸盐存在于胎盘、乳汁和血清中，后者在哺乳期内随幼鼠而下降。出生时幼鼠的血清和脑甲状腺激素降低，但在 PN2 时恢复到对照水平。暴露的幼鼠甲状腺中观察到 Nis 的显著上调。尽管血清甲状腺激素在 PN2 时恢复到对照水平，但 PN14 幼鼠大脑中的几个 TH 反应基因的表达发生了改变。成年动物的情境恐惧学习不受影响，这与之前的报告一致。血清高氯酸盐水平下降和甲状腺中 Nis 基因表达的显著上调与新生儿迅速恢复甲状腺功能正常状态一致。然而，尽管有这种恢复，胎儿期和出生时存在的血清和脑甲状腺激素不足似乎足以改变胎儿的 TH 作用，并随后改变大脑的发育轨迹。改变轨迹的生物标志物仍然存在于新生儿的大脑中，表明高氯酸盐对发育中的大脑并非没有影响。
