Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
Nutrients. 2023 Feb 20;15(4):1051. doi: 10.3390/nu15041051.
In terms of fetal muscle growth, development, and health, maternal nutrition is a crucial influence, although the exact biochemical mechanism by which this occurs is still not fully understood. To examine the potential impacts of maternal dietary restriction on fetal muscle development, the sheep maternal dietary restriction model was developed for this study. In our study, 12 pregnant ewes were evenly split into two experimental groups and fed either 75% or 100% of a maternal nutrient. In addition, a multi-omics analysis was used to study the embryonic longissimus dorsis on gestational days (GD) 85 and 135. The fetal weight at GD 135 was significantly below normal due to the maternal restricted diet ( < 0.01). When fetuses were exposed to the dietary deficit, 416 mRNAs and 40 proteins were significantly changed. At GD 85, the multi-omics analysis revealed that maternal dietary restriction led to a significant up-regulation of the cell cycle regulator gene in the cellular senescence signaling pathway, and the results of the qRT-PCR were similar to the multi-omics analysis, which showed that , , the cell cycle factors and , and the apoptosis factor were up-regulated and several skeletal muscle marker genes, such as and were down-regulated. At GD 135, maternal dietary restriction blocks the muscle fiber differentiation and maturation. The multi-omics analysis revealed that the gene was in the Hippo signaling pathway, the muscle marker genes and were significantly down-regulated, and the binding of the down-regulated gene might be potential mechanisms affecting myofiber differentiation and maturation. Knocking down the gene could inhibit the proliferation of primary embryonic myoblasts, and the expression levels of cell cycle regulatory factors and were significantly changed. Under low nutrient culture conditions, the number of myoblasts decreased and the expression of , , , and changed, which was in perfect agreement with the multi-omics analysis. All of the findings from our study helped to clarify the potential effects of maternal dietary restriction on fetal muscle growth and development. They also provided a molecular foundation for understanding the molecular regulatory mechanisms of maternal nutrition on fetal muscle growth and development, as well as for the development of new medications and the management of related metabolic diseases.
就胎儿肌肉的生长、发育和健康而言，母体营养是一个关键的影响因素，尽管这一过程的确切生化机制仍不完全清楚。为了研究母体饮食限制对胎儿肌肉发育的潜在影响，本研究建立了绵羊母体饮食限制模型。在我们的研究中，将 12 只怀孕母羊平均分为两组，分别喂食 75%或 100%的母体营养。此外，还使用多组学分析来研究妊娠第 85 天和 135 天的胚胎背最长肌。由于母体限制饮食，GD135 时胎儿体重明显低于正常水平（<0.01）。当胎儿暴露于饮食不足时，416 个 mRNA 和 40 个蛋白质发生显著变化。在 GD85 时，多组学分析表明母体饮食限制导致细胞衰老信号通路中细胞周期调节剂基因显著上调，qRT-PCR 的结果与多组学分析相似，表明、、细胞周期因子和以及凋亡因子上调，几个骨骼肌标记基因如和下调。在 GD135 时，母体饮食限制阻断肌肉纤维的分化和成熟。多组学分析表明，基因在 Hippo 信号通路中，肌肉标记基因和显著下调，下调基因的结合可能是影响肌纤维分化和成熟的潜在机制。敲低基因可以抑制原代胚胎成肌细胞的增殖，细胞周期调控因子和的表达水平发生显著变化。在低营养培养条件下，成肌细胞数量减少，、、、和的表达发生变化，这与多组学分析完全一致。我们的研究结果有助于阐明母体饮食限制对胎儿肌肉生长和发育的潜在影响。它们还为了解母体营养对胎儿肌肉生长和发育的分子调控机制提供了分子基础，也为开发新的药物和管理相关代谢疾病提供了依据。
