Stoate Katharine L, Harris Muriel J, Juriloff Diana M
Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Birth Defects Res A Clin Mol Teratol. 2008 Oct;82(10):720-7. doi: 10.1002/bdra.20497.
The SELH/Bc mouse strain has a high risk of the NTD, exencephaly, caused by multifactorial genetics. All SELH/Bc embryos have delayed elevation of neural folds; some never elevate (future exencephalics). Maternal diets affect SELH/Bc exencephaly rates: 25-35% on Purina Diet 5015 versus 5-10% on Purina Diet 5001. We hypothesized that in SELH/Bc, the diets affect maternal blood glucose and embryonic developmental rate.
We compared mice fed the two diets. On GD 9.4 we tested maternal blood glucose and examined embryos for developmental age (somite count) and cranial neural fold morphology. We observed GD 14 exencephaly rates.
Diet 5015 caused fivefold more exencephaly (40 vs. 7% on GD 14), significantly higher mean maternal blood glucose in replicate experiments (6.3 vs. 5.5, p < .05; 6.3 vs. 5.3 mmol/L, p < .05), and significantly higher mean litter somite count on GD 9.4 (18.4 vs. 15.0, p < .05; 16.7 vs. 14.4 somites, p < .05). Among midrange embryos (15-16 somites), embryos from Diet 5015 were significantly shifted to earlier stages of midbrain fold morphology and had significantly more distance between the tips of the folds (p < .05).
In SELH/Bc mice, the 5015 diet causes higher maternal blood glucose, a faster overall embryonic developmental rate during neural tube closure, and delayed midbrain fold elevation relative to overall development. This pattern suggests that maternal dietary effects that modestly increase embryonic growth rate may exacerbate a lack of coordination between genetically delayed neural folds and normally developing underlying tissues, increasing risk of NTD.
SELH/Bc小鼠品系因多因素遗传而有患神经管缺陷（NTD）——脑膨出的高风险。所有SELH/Bc胚胎的神经褶抬高均延迟；有些胚胎的神经褶从未抬高（未来会发生脑膨出）。母体饮食会影响SELH/Bc小鼠的脑膨出率：食用普瑞纳5015饲料时脑膨出率为25% - 35%，而食用普瑞纳5001饲料时为5% - 10%。我们推测，在SELH/Bc小鼠中，饮食会影响母体血糖和胚胎发育速率。
我们比较了喂食两种饲料的小鼠。在妊娠第9.4天，我们检测了母体血糖，并检查胚胎的发育年龄（体节计数）和颅神经褶形态。我们观察了妊娠第14天的脑膨出率。
5015饲料导致的脑膨出率高出五倍（妊娠第14天分别为40%和7%），在重复实验中母体平均血糖显著更高（分别为6.3和5.5，p < 0.05；6.3和5.3 mmol/L，p < 0.05），且在妊娠第9.4天平均窝仔体节计数显著更高（分别为18.4和15.0，p < 0.05；16.7和14.4体节，p < 0.05）。在中等体节数（15 - 16个）的胚胎中，来自5015饲料组的胚胎中脑褶形态显著提前，且褶尖之间的距离显著更大（p < 0.05）。
在SELH/Bc小鼠中，5015饲料导致母体血糖升高，在神经管闭合期间整体胚胎发育速率加快，且相对于整体发育，中脑褶抬高延迟。这种模式表明，适度提高胚胎生长速率的母体饮食效应可能会加剧基因导致的神经褶延迟与正常发育的下层组织之间缺乏协调性，从而增加神经管缺陷的风险。
