Department of Occupational Health, Faculty of Preventive Medicine, Third Military Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China.
Neurotox Res. 2011 Jul;20(1):15-25. doi: 10.1007/s12640-010-9214-y. Epub 2010 Aug 14.
Hyperthyroidism is prevalent during pregnancy, but little is known about the effects of excess thyroid hormone on the development of embryonic neural stem/progenitor cells (NSCs), and the mechanisms underlying these effects. Previous studies indicate that STAT3 plays a crucial role in determining NSC fate during neurodevelopment. In this study, we investigated the effects of a supraphysiological dose of 3,5,3'-L-triiodothyronine (T3) on the proliferation and maintenance of NSCs derived from embryonic day 13.5 mouse neocortex, and the involvement of STAT3 in this process. Our results suggest that excess T3 treatment inhibits NSC proliferation and maintenance. T3 decreased tyrosine phosphorylation of JAK1, JAK2 and STAT3, and subsequently inhibited STAT3-DNA binding activity. Furthermore, proliferation and maintenance of NSCs were decreased by inhibitors of JAKs and STAT3, indicating that the STAT3 signalling pathway is involved in the process of NSC proliferation and maintenance. Taken together, these results suggest that the STAT3 signalling pathway is involved in the process of T3-induced inhibition of embryonic NSC proliferation and maintenance. These findings provide data for understanding the effects of hyperthyroidism during pregnancy on fetal brain development, and the mechanisms underlying these effects.
甲状腺功能亢进症在妊娠期间很常见，但对于过多的甲状腺激素对胚胎神经干细胞/祖细胞（NSC）发育的影响以及这些影响的机制知之甚少。先前的研究表明，STAT3 在神经发育过程中决定 NSC 命运方面起着至关重要的作用。在这项研究中，我们研究了超生理剂量的 3,5,3'-L-三碘甲状腺原氨酸（T3）对源自胚胎第 13.5 天小鼠新皮层的 NSC 的增殖和维持的影响，以及 STAT3 在该过程中的参与情况。我们的结果表明，过量的 T3 处理会抑制 NSC 的增殖和维持。T3 降低了 JAK1、JAK2 和 STAT3 的酪氨酸磷酸化，随后抑制了 STAT3-DNA 结合活性。此外，JAK 和 STAT3 的抑制剂降低了 NSC 的增殖和维持，表明 STAT3 信号通路参与了 NSC 增殖和维持的过程。总之，这些结果表明 STAT3 信号通路参与了 T3 诱导的胚胎 NSC 增殖和维持抑制的过程。这些发现为理解妊娠期间甲状腺功能亢进对胎儿大脑发育的影响以及这些影响的机制提供了数据。
