Folate, a cofactor for the supply of one‐carbon groups, is required by epigenetic processes to regulate cell lineage determination during development. The intake of folic acid (FA), the synthetic form of folate, has increased significantly over the past decade, but the effects of high periconceptional FA intake on cell lineage determination in the early embryo remains unknown. Here, we investigated the effect of maternal high FA (HFA) intake on blastocyst development and expression of key regulatory genes. C57BL/6 adult female mice were fed either Control diet (1 mg FA) for 4 weeks before conception and during the preimplantation period (Con‐Con); Control diet for 4 weeks preconception, followed by HFA (5 mg FA) diet during preimplantation (Con‐HFA); or HFA diet for 4 weeks preconception and during preimplantation (HFA‐HFA). At E3.5, blastocyst cell number, protein, and mRNA expression were measured. In HFA‐HFA blastocysts, trophectoderm cell numbers and expression of CDX2, Oct‐4, and Nanog were reduced compared with Con‐Con blastocysts; Con‐HFA blastocysts showed lower CDX2 and Oct‐4 expression than Con‐Con blastocysts. These findings suggest periconceptional HFA intake induces changes in key regulators of embryo morphogenesis with potential implications for subsequent development.

中文翻译：

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受孕前后母体叶酸摄入量高会改变小鼠囊胚谱系分配和关键发育调控基因的表达

叶酸是提供单碳基团的辅助因子，是表观遗传过程所必需的，以调节发育过程中的细胞谱系决定。在过去十年中，叶酸的合成形式叶酸 (FA) 的摄入量显着增加，但围孕期 FA 摄入量高对早期胚胎细胞谱系测定的影响仍然未知。在这里，我们研究了母体高 FA (HFA) 摄入对囊胚发育和关键调控基因表达的影响。C57BL/6 成年雌性小鼠在受孕前和植入前阶段 (Con-Con) 喂食对照饮食 (1 mg FA) 4 周；孕前控制饮食 4 周，然后在植入前 (Con-HFA) 期间进行 HFA（5 毫克 FA）饮食；或 HFA 饮食 4 周孕前和植入前 (HFA-HFA)。在 E3.5，测量囊胚细胞数、蛋白质和mRNA表达。在 HFA-HFA 囊胚中，滋养外胚层细胞数量和 CDX2 的表达，与 Con-Con 囊胚相比，Oct-4和Nanog减少；Con-HFA 囊胚的 CDX2 和Oct-4表达低于 Con-Con 囊胚。这些发现表明围孕期 HFA 摄入诱导胚胎形态发生的关键调节因子发生变化，对后续发育具有潜在影响。