Maternal nutrition is pivotal for proper fetal development, with one-carbon metabolites (OCM) playing a key role in fetal epigenetic programming through DNA and histone methylation. The study aimed to investigate the effects of nutrient restriction and OCM supplementation on fetal liver metabolomics in pregnant beef-heifers, focusing on metabolites and pathways associated with amino acid, vitamin and cofactor, carbohydrate, and energy metabolism at day 63 of gestation. Thirty-one crossbred Angus heifers were artificially inseminated and allocated to 4 nutritional treatments in a 2 × 2 factorial arrangement of treatments, with the 2 factors being dietary intake/rate of gain (control-diet [CON]; 0.60 kg/d ADG, vs. restricted-diet [RES]; −0.23 kg/d ADG) and OCM supplementation (supplemented [+OCM] vs. not supplemented [−OCM]). The resulting treatment groups—CON − OCM, CON + OCM, RES − OCM, and RES + OCM were maintained for 63 day post-breeding. Following this period, fetal liver tissues were collected and subjected to metabolomic analysis using UPLC-tandem mass-spectrometry. We identified 288 metabolites, with the majority (n = 54) being significantly influenced by the main effect of gain (P ≤ 0.05). Moreover, RES showed decreased abundances of most metabolites in pathways such as lysine metabolism; leucine, isoleucine, and valine metabolism; and tryptophan metabolism, compared to CON. Supplementation with OCM vs. no OCM supplementation, resulted in greater abundance of metabolites (P ≤ 0.05) affecting pathways associated with methionine, cysteine, S-adenosylmethionine and taurine metabolism; guanidino and acetamido metabolism; and nicotinate and nicotinamide metabolism. Notably, OCM supplementation with a moderate rate of gain increased the concentrations of ophthalmate, N-acetylglucosamine, and ascorbic-acid 3-sulfate, which are important for proper fetal development (P ≤ 0.05). Nutrient restriction reduced the majority of liver metabolites, while OCM supplementation increased a smaller number of metabolites. Thus, OCM supplementation may be protective of metabolite concentrations in key developmental pathways, which could potentially enhance fetal development under nutrient-restricted conditions.

中文翻译：

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一碳代谢物补充和营养限制会改变肉牛妊娠早期胎儿肝脏代谢组学特征


母体营养对于胎儿的正常发育至关重要，一碳代谢物 （OCM） 通过 DNA 和组蛋白甲基化在胎儿表观遗传编程中起着关键作用。该研究旨在调查营养限制和 OCM 补充剂对怀孕小母牛胎儿肝脏代谢组学的影响，重点关注妊娠第 63 天与氨基酸、维生素和辅因子、碳水化合物和能量代谢相关的代谢物和途径。对 31 头杂交安格斯小母牛进行人工授精，并以 2 × 2 因子处理安排分配到 4 种营养处理中，其中 2 个因素是饮食摄入量/增重率（对照饮食 [CON];0.60 kg/d ADG，与限制饮食 [RES];-0.23 kg/d ADG）和 OCM 补充剂（补充 [+OCM] 与未补充 [−OCM]）。所得处理组 — CON − OCM、CON + OCM、RES − OCM 和 RES + OCM 在育种后维持 63 天。在此期间，收集胎儿肝组织并使用 UPLC 串联质谱法进行代谢组学分析。我们鉴定了 288 种代谢物，其中大多数 （n = 54） 受增益主效应的显著影响 （P ≤ 0.05）。此外，RES 显示赖氨酸代谢等途径中大多数代谢物的丰度降低;亮氨酸、异亮氨酸和缬氨酸代谢;和 CON 相比，补充 OCM 与不补充 OCM 导致影响与蛋氨酸、半胱氨酸、S-腺苷甲硫氨酸和牛磺酸代谢相关的途径的代谢物丰度更高 （P ≤ 0.05）;胍和啶虫胺代谢;以及烟酸和烟酰胺代谢。 值得注意的是，补充适度增重的 OCM 增加了眼球酸盐、N-乙酰葡萄糖胺和抗坏血酸 3-硫酸盐的浓度，这些对胎儿的正常发育很重要 （P ≤ 0.05）。营养限制减少了大部分肝脏代谢物，而 OCM 补充剂增加了少量代谢物。因此，补充 OCM 可能保护关键发育途径中的代谢物浓度，这可能会在营养受限的条件下促进胎儿发育。