Periconceptional folic acid (FA) supplementation not only reduces the incidence of neural tube defects, but also improves cognitive performances in offspring. However, the genes or pathways that are epigenetically regulated by FA in neurodevelopment were rarely reported. To elucidate the underlying mechanism, the effect of FA on the methylation profiles in brain tissue of male rat offspring was assessed by methylated DNA immunoprecipitation chip. Differentially methylated genes (DMGs) and gene network analysis were identified using DAVID and KEGG pathway analysis. Compared with the folate-normal diet group, 1939 DMGs were identified in the folate-deficient diet group, and 1498 DMGs were identified in the folate-supplemented diet group, among which 298 DMGs were overlapped. The pathways associated with neurodevelopment and learning/memory abilities were differentially methylated in response to maternal FA intake during pregnancy, and there were some identical and distinctive potential mechanisms under FA deficiency or FA-supplemented conditions. In conclusion, genes and pathways associated with neurodevelopment and learning/memory abilities were differentially methylated in male rat offspring in response to maternal FA deficiency or supplementation during pregnancy.

中文翻译：

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母体叶酸影响雄性大鼠后代的DNA甲基化谱，与神经发育和学习/记忆能力有关

孕周叶酸（FA）的补充不仅减少了神经管缺陷的发生率，而且还提高了后代的认知能力。但是，很少有人报道在神经发育中受FA表观遗传调控的基因或途径。为了阐明其潜在机制，通过甲基化DNA免疫沉淀芯片评估了FA对雄性大鼠后代脑组织甲基化谱的影响。使用DAVID和KEGG途径分析鉴定了差异甲基化基因（DMG）和基因网络分析。与叶酸正常饮食组相比，叶酸缺乏饮食组中鉴定出1939 DMGs，补充叶酸饮食组中鉴定出1498 DMG，其中298重叠。妊娠期间母体FA的摄入与神经发育和学习/记忆能力相关的途径甲基化程度不同，在FA缺乏或FA补充的情况下，存在一些相同且独特的潜在机制。总之，响应母体FA缺乏或怀孕期间补充，雄性大鼠后代中与神经发育和学习/记忆能力有关的基因和途径被甲基化。