Department of Human Genetics, McGill University, Montreal Children's Hospital Research Institute, Montreal, Canada.
Am J Clin Nutr. 2010 Apr;91(4):1035-43. doi: 10.3945/ajcn.2009.28754. Epub 2010 Feb 17.
Embryonic development may be compromised by dietary and genetic disruptions in folate metabolism because of the critical role of folate in homocysteine metabolism, methylation, and nucleotide synthesis. Methylenetetrahydrofolate reductase (MTHFR), choline, and riboflavin play distinct roles in homocysteine detoxification and generation of one-carbon donors for methylation. The effect of low dietary choline and riboflavin on pregnancy complications and heart development has not been adequately addressed.
Our goal was to determine whether dietary deficiencies of choline and riboflavin in pregnant mice, with and without mild MTHFR deficiency, affect embryonic development.
Female Mthfr(+/+) and Mthfr(+/-) mice were fed a control diet (CD), a choline-deficient diet (ChDD), or a riboflavin-deficient diet (RbDD) and were then mated with male Mthfr(+/-) mice. Embryos were collected 14.5 d postcoitum and examined for reproductive outcomes and cardiac defects.
Plasma homocysteine was higher in ChDD- than in CD-fed females. Liver MTHFR enzyme activity was greater in ChDD-fed Mthfr(+/+) than in CD-fed Mthfr(+/+) females. The RbDD resulted in a higher percentage of delayed embryos and smaller embryos than did the CD. There were more heart defects, which were all ventricular septal defects, in embryos from the ChDD- and RbDD-fed females than from the CD-fed females. Dietary riboflavin and MTHFR deficiency resulted in decreased left ventricular wall thickness in embryonic hearts compared with embryos from CD-fed Mthfr(+/+) females.
Low dietary choline and riboflavin affect embryonic growth and cardiac development in mice. Adequate choline and riboflavin may also play a role in the prevention of these pregnancy complications in women.
由于叶酸在同型半胱氨酸代谢、甲基化和核苷酸合成中的关键作用，饮食和遗传因素对叶酸代谢的干扰可能会影响胚胎发育。亚甲基四氢叶酸还原酶（MTHFR）、胆碱和核黄素在同型半胱氨酸解毒和生成甲基供体方面发挥着不同的作用。低膳食胆碱和核黄素对妊娠并发症和心脏发育的影响尚未得到充分解决。
我们的目标是确定在轻度 MTHFR 缺乏的情况下，妊娠小鼠的膳食胆碱和核黄素缺乏是否会影响胚胎发育。
雌性 Mthfr(+/+)和 Mthfr(+/-)小鼠分别喂食对照饮食（CD）、胆碱缺乏饮食（ChDD）或核黄素缺乏饮食（RbDD），然后与雄性 Mthfr(+/-)小鼠交配。胚胎于交配后 14.5 天收集，检查生殖结果和心脏缺陷。
ChDD 喂养的雌性血浆同型半胱氨酸高于 CD 喂养的雌性。ChDD 喂养的 Mthfr(+/+)雌性肝脏 MTHFR 酶活性高于 CD 喂养的 Mthfr(+/+)雌性。与 CD 相比，RbDD 导致更多的胚胎延迟和更小的胚胎。与 CD 喂养的雌性相比，来自 ChDD 和 RbDD 喂养的雌性的胚胎有更多的心脏缺陷，均为室间隔缺损。与 CD 喂养的 Mthfr(+/+)雌性胚胎相比，膳食核黄素和 MTHFR 缺乏导致胚胎心脏左心室壁厚度减小。
低膳食胆碱和核黄素会影响小鼠胚胎的生长和心脏发育。足够的胆碱和核黄素可能在预防这些妊娠并发症方面也发挥作用。
