Comer C P, Norton S
Neurotoxicology. 1985 Fall;6(3):25-35.
Rat pups were made hypothyroid by administration of the antithyroid agent, methimazole, to pregnant and lactating dams from gestational day 17 to postnatal day 10. Dendritic branching of caudate neurons in methimazole-treated pups was decreased 30 to 40 percent between 1 and 28 days of age. Perinatal methimazole treatment produced a pattern of developmental deficit or prolonged delay in the growth of dendrites of caudate interneurons. The antithyroid effect was also apparent in morphometric changes in the thyroid gland of methimazole-treated rats. Functional tissue was present at all ages examined. Colloid storage in the thyroid was decreased during methimazole administration compared with colloid storage after methimazole was discontinued. Both during and after methimazole administration the size of thyroid follicular cell nuclei in methimazole-treated pups was significantly greater than that of thyroid nuclei in control animals. Changes in dendritic branching, body weight and thyroxine levels lasted into adult life but recovery toward control levels was seen in adults. These changes in offspring following maternal administration of a goitrogen were demonstrated at an exposure level well below complete thyroid suppression.
从妊娠第17天至出生后第10天,给怀孕和哺乳期的母鼠施用抗甲状腺药物甲巯咪唑,使幼鼠甲状腺功能减退。在1至28日龄之间,用甲巯咪唑处理的幼鼠尾状核神经元的树突分支减少了30%至40%。围产期甲巯咪唑治疗导致尾状核中间神经元树突生长出现发育缺陷或长期延迟的模式。抗甲状腺作用在甲巯咪唑处理的大鼠甲状腺的形态测量变化中也很明显。在所有检查的年龄阶段都存在功能性组织。与停用甲巯咪唑后的胶体储存相比,在施用甲巯咪唑期间甲状腺中的胶体储存减少。在施用甲巯咪唑期间和之后,用甲巯咪唑处理的幼鼠甲状腺滤泡细胞核的大小明显大于对照动物的甲状腺核。树突分支、体重和甲状腺素水平的变化持续到成年期,但成年后可见向对照水平恢复。在远低于完全抑制甲状腺的暴露水平下,证明了母体施用致甲状腺肿物质后后代的这些变化。