过量叶酸对小鼠胚胎发育及Vangl1基因表达的影响

Effects of Excessive Folic Acid on Embryonic Development and Vangl1 Gene Expression in Mice

  • 摘要: 为探究过量叶酸对胚胎发育期Vangl1基因表达量、胚胎及神经管发育的影响,通过对昆明小鼠饲喂过量叶酸(4倍标准量),观察和分析胚胎/胎儿发育情况及神经管闭合的组织学状况;采用逆转录酶PCR(RT-PCR)检测,探讨了平面细胞极性途径信号通路中重要基因Vangl1基因表达情况。结果表明:过量叶酸添加易导致卵裂速度过快、不同程度的胚胎退化、发育与胚龄不一致等发育异常,胎儿发育也呈现颅脑顶部未闭合、脊椎裂、发育迟缓等畸形情况。在小鼠怀孕初期E1.0~E2.5时,无法检测出Vangl1基因或表达水平较低;在E9.5、E10.5、E11.5,相比标准叶酸添加而言,过量叶酸组的Vangl1基因同期表达显著下调(P<0.05)。因此,围产期补充过量叶酸对胚胎/胎儿发育产生不利影响,同时对神经管发育相关的重要基因Vangl1表达有一定的抑制作用。

     

    Abstract: The aim of this study is to investigate the effects of Vangl1 gene expression and on embryonic development, neural tube development by excessive folate in embryonic development. The study was carried out by adding excess folic acid (4 times the standard amount) in KM mouse feed. Then, observe the change of mouse embryo/fetal development and neural tube closure. At the same time, to explore the expression of the Vangl1 gene that is important in the planar cell polarity (PCP) signaling pathway by reverse transcriptase PCR (RT-PCR). As shown in results: due to the addition of excess folic acid, mouse cleavage rate was too fast, different degrees of embryo degradation, development and embryonic age were inconsistent, and fetal development also shows the top of the brain was not closed, spina bifida, stunting and other malformations. At the molecular level, the pregnant mice were unable to detect the Vangl1 gene or the expression level was low from embryonic day (E)1.0 to E2.5, and the Vangl1 gene expression was down-regulated (P<0.05) of excess folic acid mice compare with standard group on E9.5, E10.5 and E11.5. These findings suggest that excessive folic acid supplementation will cause adverse effects for embryo/fetal development during the perinatal period, while having a certain inhibitory effect on Vangl 1 expression which has close relationship with neural tube development.

     

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