Li Deqiang, Rozen Rima
Departments of Human Genetics, Pediatrics, and Biology, McGill University-Montreal Children's Hospital Research Institute, Montreal, PQ, Canada.
J Nutr. 2006 Jul;136(7):1774-8. doi: 10.1093/jn/136.7.1774.
Low dietary folate and deficiency of methylenetetrahydrofolate reductase (Mthfr) were reported to increase the risk for congenital heart defects, but contributory mechanisms have not been elucidated. Because low folate and absent MTHFR activity were shown to affect proliferation and apoptosis in developing neural tissue, we examined these processes in the myocardium of embryos from Mthfr +/+ and Mthfr +/- mice fed control diets (CD) or folic acid-deficient diets (FADD). Mice consumed the designated diets for 8 wk, from weaning and through pregnancy until they were killed. Embryos were assessed on gestational day 12.5 for myocardial proliferation by 5-bromo-2'-deoxyuridine (BrdU) labeling and for apoptosis by TdT-mediated dUTP nick end labeling staining and caspase 3/7 activity assays. FADD-treated dams had significantly higher resorption rates than CD-treated dams. Embryonic lengths and weights from FADD-treated dams were significantly lower than those from CD-treated dams; the smallest embryos were those of the Mthfr +/- dams that consumed the FADD, with effect of genotype tending to be significant (P = 0.09). The thickness of cardiac ventricular compact walls of embryos from FADD-treated dams was significantly reduced, and embryonic myocardium from FADD-treated dams had significantly fewer BrdU-labeled cells compared with CD-treated dams, with no differences in apoptosis due to the diets. Genotype did not affect proliferation or apoptosis. Our results suggest that proliferation of embryonic myocardium is sensitive to maternal dietary folate and that folate supplementation during pregnancy is important for normal heart development and prevention of heart defects.
据报道，膳食中叶酸含量低以及亚甲基四氢叶酸还原酶（Mthfr）缺乏会增加先天性心脏缺陷的风险，但具体作用机制尚未阐明。由于低叶酸和MTHFR活性缺乏会影响发育中的神经组织的增殖和凋亡，我们研究了喂食对照饮食（CD）或叶酸缺乏饮食（FADD）的Mthfr +/+和Mthfr +/-小鼠胚胎心肌中的这些过程。小鼠从断奶后开始食用指定饮食8周，直至怀孕并被处死。在妊娠第12.5天，通过5-溴-2'-脱氧尿苷（BrdU）标记评估胚胎心肌增殖情况，并通过TdT介导的dUTP缺口末端标记染色和半胱天冬酶3/7活性测定评估凋亡情况。接受FADD处理的母鼠的吸收率明显高于接受CD处理的母鼠。接受FADD处理的母鼠所产胚胎的长度和重量明显低于接受CD处理的母鼠；最小的胚胎是食用FADD的Mthfr +/-母鼠所产的，基因型的影响趋于显著（P = 0.09）。与接受CD处理的母鼠相比，接受FADD处理的母鼠所产胚胎的心室致密壁厚度明显减小，且接受FADD处理的母鼠所产胚胎心肌中BrdU标记的细胞明显减少，饮食对凋亡无差异。基因型不影响增殖或凋亡。我们的结果表明，胚胎心肌增殖对母体膳食叶酸敏感，孕期补充叶酸对心脏正常发育和预防心脏缺陷很重要。
