Hawes Jazmin E, Tesic Dijana, Whitehouse Andrew J, Zosky Graeme R, Smith Jeremy T, Wyrwoll Caitlin S
School of Anatomy, Physiology and Human Biology, The University of Western Australia, Perth 6009, Australia.
Telethon Kids Institute, The University of Western Australia, Perth 6009, Australia.
Behav Brain Res. 2015 Jun 1;286:192-200. doi: 10.1016/j.bbr.2015.03.008. Epub 2015 Mar 7.
Prenatal exposure to vitamin D is thought to be critical for optimal fetal neurodevelopment, yet vitamin D deficiency is apparent in a growing proportion of pregnant women. The aim of this study was to determine whether a mouse model of vitamin D-deficiency alters fetal neurodevelopment. Female BALB/c mice were placed on either a vitamin D control (2,195 IU/kg) or deficient (0 IU/kg) diet for 5 weeks prior to and during pregnancy. Fetal brains were collected at embryonic day (E) 14.5 or E17.5 for morphological and gene expression analysis. Vitamin D deficiency during pregnancy reduced fetal crown-rump length and head size. Moreover, lateral ventricle volume was reduced in vitamin D-deficient foetuses. Expression of neurotrophin genes brain-derived neurotrophic factor (Bdnf) and transforming growth factor-β1 (Tgf-β1) was altered, with Bdnf reduced at E14.5 and increased at E17.5 following vitamin D deficiency. Brain expression of forkhead box protein P2 (Foxp2), a gene known to be important in human speech and language, was also altered. Importantly, Foxp2 immunoreactive cells in the developing cortex were reduced in vitamin D-deficient female foetuses. At E17.5, brain tyrosine hydroxylase (TH) gene expression was reduced in females, as was TH protein localization (to identify dopamine neurons) in the substantia nigra of vitamin D-deficient female foetuses. Overall, we show that prenatal vitamin D-deficiency leads to alterations in fetal mouse brain morphology and genes related to neuronal survival, speech and language development, and dopamine synthesis. Vitamin D appears to play an important role in mouse neurodevelopment.
产前暴露于维生素D被认为对胎儿最佳神经发育至关重要，但维生素D缺乏在越来越多的孕妇中明显存在。本研究的目的是确定维生素D缺乏的小鼠模型是否会改变胎儿神经发育。雌性BALB/c小鼠在怀孕前及怀孕期间被置于维生素D对照（2,195 IU/kg）或缺乏（0 IU/kg）饮食中5周。在胚胎第14.5天（E14.5）或E17.5收集胎儿大脑进行形态学和基因表达分析。孕期维生素D缺乏会降低胎儿的顶臀长度和头部大小。此外，维生素D缺乏的胎儿侧脑室体积减小。神经营养因子基因脑源性神经营养因子（Bdnf）和转化生长因子-β1（Tgf-β1）的表达发生改变，维生素D缺乏后，Bdnf在E14.5时降低，在E17.5时升高。叉头框蛋白P2（Foxp2）的脑表达也发生改变，该基因在人类言语和语言中很重要。重要的是，维生素D缺乏的雌性胎儿发育中的皮质中Foxp2免疫反应性细胞减少。在E17.5时，雌性小鼠脑酪氨酸羟化酶（TH）基因表达降低，维生素D缺乏的雌性胎儿黑质中TH蛋白定位（用于识别多巴胺能神经元）也降低。总体而言，我们表明产前维生素D缺乏会导致胎儿小鼠脑形态以及与神经元存活、言语和语言发育及多巴胺合成相关的基因发生改变。维生素D似乎在小鼠神经发育中起重要作用。
