Department of Natural Sciences, University of South Carolina Beaufort, Bluffton, SC 29909, USA.
Neurotoxicology. 2012 Oct;33(5):1322-9. doi: 10.1016/j.neuro.2012.08.008. Epub 2012 Sep 2.
Humans and wildlife are exposed to environmental pollutants that have been shown to interfere with the thyroid hormone system and thus may affect brain development. Our goal was to expose pregnant rats to propylthiouracil (PTU) to measure the effects of a goitrogen on white matter development in offspring using magnetic resonance imaging (MRI) and volumetric analysis. We exposed pregnant Sprague Dawley (SD) rats to 3 or 10 ppm PTU from gestation day 7 (GD7) until postnatal day 25 (P25) to determine the effects on white matter (WM), gray matter (GM), and hippocampus volumes in offspring. We sacrificed offspring at P25 but continued the life of some offspring to P90 to measure persistent effects in adult animals. P25 offspring exposed to 10 ppm PTU displayed lowered levels of triiodothyronine (T3) and thyroxine (T4); cerebral WM, GM, and total brain volumes were significantly lower than the volumes in control animals. P90 adults exposed to 10 ppm PTU displayed normal T3 levels but lowered T4 levels; WM, GM, total brain, and hippocampal volumes were significantly lower than the volumes in control adults. Both P25 and P90 rats exposed to 10 ppm PTU displayed significant reductions in percent WM as well as heterotopias in the corpus callosum. Exposure to 3 ppm PTU did not produce any significant effects. These results suggest that MRI coupled with volumetric analysis is a powerful tool in assessing the effects of thyroid hormone disruption on white matter development and brain structure. This approach holds great promise in assessing neurotoxicity of xenobiotics in humans and wildlife.
人类和野生动物暴露于环境污染物中，这些污染物已被证明会干扰甲状腺激素系统，从而可能影响大脑发育。我们的目标是用丙基硫氧嘧啶（PTU）处理怀孕的大鼠，以使用磁共振成像（MRI）和体积分析来测量致甲状腺肿剂对后代白质发育的影响。我们从妊娠第 7 天（GD7）到产后第 25 天（P25）使怀孕的 Sprague Dawley（SD）大鼠暴露于 3 或 10ppm 的 PTU，以确定对后代白质（WM）、灰质（GM）和海马体积的影响。我们在 P25 处死后代，但继续一些后代的生命到 P90，以测量成年动物中的持续影响。暴露于 10ppm PTU 的 P25 后代表现出三碘甲状腺原氨酸（T3）和甲状腺素（T4）水平降低；大脑 WM、GM 和总脑体积明显低于对照动物的体积。暴露于 10ppm PTU 的 P90 成年动物表现出正常的 T3 水平但 T4 水平降低；WM、GM、总脑和海马体积明显低于对照成年动物的体积。暴露于 10ppm PTU 的 P25 和 P90 大鼠 WM 的百分比以及胼胝体的异位明显减少。暴露于 3ppm PTU 没有产生任何显著影响。这些结果表明，MRI 结合体积分析是评估甲状腺激素破坏对白质发育和大脑结构影响的有力工具。这种方法在评估人类和野生动物中异生物质的神经毒性方面具有很大的潜力。
