Genomic imprinting is important for mammalian development and its dysregulation can cause various developmental defects and diseases. The study evaluated the effects of different dietary combinations of folic acid and B12 on epigenetic regulation of IGF2R and KCNQ1OT1 ncRNA in C57BL/6 mice model. Female mice were fed diets with nine combinations of folic acid and B12 for 4 weeks. They were mated and off-springs born (F1) were continued on the same diet for 6 weeks postweaning and were allowed to mate. The placenta and fetal (F2) tissues were collected at day 20 of gestation. Dietary deficiency of folate (BNFD and BOFD) and B12 (BDFN) with either state of other vitamin or combined deficiency of both vitamins (BDFD) in comparison to BNFN, were overall responsible for reduced expression of IGF2R in the placenta (F1) and the fetal liver (F2) whereas a combination of folate deficiency with different levels of B12 revealed sex-specific differences in kidney and brain. The alterations in the expression of IGF2R caused by folate-deficient conditions (BNFD and BOFD) and both deficient condition (BDFD) was found to be associated with an increase in suppressive histone modifications. Over-supplementation of either folate or B12 or both vitamins in comparison to BNFN, led to increase in expression of IGF2R and KCNQ1OT1 in the placenta and fetal tissues. The increase in the expression of IGF2R caused by folate over-supplementation (BNFO) was associated with decreased DNA methylation in fetal tissues. KCNQ1OT1 noncoding RNA (ncRNA), however, showed upregulation under deficient conditions of folate and B12 only in female fetal tissues which correlated well with hypomethylation observed under these conditions. An epigenetic reprograming of IGF2R and KCNQ1OT1 ncRNA in the offspring was evident upon different dietary combinations of folic acid and B12 in the mice.

中文翻译：

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父母饮食中叶酸和维生素 B12 的不同饮食组合导致小鼠胎盘和胎儿组织中 IGF2R 和 KCNQ1OT1 的表观遗传重编程

基因组印记对哺乳动物的发育很重要，其失调会导致各种发育缺陷和疾病。该研究评估了叶酸和 B12 的不同饮食组合对 C57BL/6 小鼠模型中 IGF2R 和 KCNQ1OT1 ncRNA 表观遗传调控的影响。给雌性小鼠喂食含有 9 种叶酸和 B12 组合的饮食，持续 4 周。它们被交配，出生的后代 (F1) 在断奶后继续使用相同的饮食 6 周，并被允许交配。在妊娠第 20 天收集胎盘和胎儿 (F2) 组织。与 BNFN 相比，叶酸（BNFD 和 BOFD）和 B12（BDFN）的膳食缺乏与其他维生素的任一状态或两种维生素的联合缺乏（BDFD），总体上是导致胎盘 (F1) 和胎儿肝脏 (F2) 中 IGF2R 表达降低的原因，而叶酸缺乏与不同水平的 B12 的组合揭示了肾脏和大脑中的性别特异性差异。发现由叶酸缺乏条件（BNFD 和 BOFD）和两种缺乏条件（BDFD）引起的 IGF2R 表达的改变与抑制性组蛋白修饰的增加有关。与 BNFN 相比，过量补充叶酸或 B12 或两种维生素会导致胎盘和胎儿组织中 IGF2R 和 KCNQ1OT1 的表达增加。叶酸过度补充 (BNFO) 引起的 IGF2R 表达增加与胎儿组织中 DNA 甲基化减少有关。然而，KCNQ1OT1 非编码 RNA (ncRNA) 仅在雌性胎儿组织中在叶酸和 B12 缺乏条件下显示上调，这与在这些条件下观察到的低甲基化密切相关。在小鼠中叶酸和 B12 的不同饮食组合下，后代中 IGF2R 和 KCNQ1OT1 ncRNA 的表观遗传重编程是显而易见的。