Maternal nutrient restriction causes small for gestational age (SGA) offspring, which exhibit a higher risk for metabolic syndrome in adulthood. Fetal skeletal muscle is particularly sensitive to maternal nutrient restriction, which impairs muscle mass and metabolism. Using a 50% nutrient restriction treatment from gestational day (GD) 35 to GD 135 in sheep, we routinely observe a spectral phenotype of fetal weights within the nutrient-restricted (NR) group. Thus, our objective was to evaluate the effect of maternal NR on muscle mass, myofiber hypertrophy, myonuclear dotation, and molecular markers for protein synthesis and degradation, while accounting for the observed fetal weight variation. Within the NR group, we classified upper-quartile fetuses into NR(Non-SGA) (n = 11) and lower-quartile fetuses into NR(SGA) (n = 11). A control group (n = 12) received 100% of nutrient requirements throughout pregnancy. At GD 135, fetal plasma and organs were collected, and gastrocnemius and soleus muscles were sampled for investigation. Results showed decreased (P < 0.05) absolute tissue/organ weights, including soleus and gastrocnemius muscles, in NR(SGA) fetuses compared to NR(Non-SGA) and control. Myofiber cross-sectional area was smaller in NR(SGA) vs control for gastrocnemius (P = 0.0092) and soleus (P = 0.0097) muscles. Within the gastrocnemius muscle, the number of myonuclei per myofiber was reduced (P = 0.0442) in NR(SGA) compared to control. Cortisol may induce protein degradation. However, there were no differences in fetal cortisol among groups. Nevertheless, for gastrocnemius muscle, cortisol receptor (NR3C1; P = 0.0124), and FOXO1 (P = 0.0131) were upregulated in NR(SGA) compared to control while NR(Non-SGA) did not differ from the other 2 groups. KLF15 was upregulated (P = 0.0002) in both NR(SGA) and NR(Non-SGA); while FBXO32, TRIM63, BCAT2 or MSTN did not differ. For soleus muscle, KLF15 mRNA was upregulated (P = 0.0145) in NR(SGA) compared to control, and expression of MSTN was increased (P = 0.0259) in NR(SGA) and NR(Non-SGA) compared to control. At the protein level, none of the mentioned molecules nor total ubiquitin-labeled proteins differed among groups (P > 0.05). Indicators of protein synthesis (total and phosphorylated MTOR, EI4EBP1, and RPS6KB1) did not differ among groups in either muscle (P > 0.05). Collectively, results highlight that maternal NR unequally affects muscle mass in NR(SGA) and NR(Non-SGA) fetuses, and alterations in myofiber cross-sectional area and myonuclei number partially explain those differences.

母亲的营养限制会导致小于胎龄（SGA）的后代，这些后代在成年后表现出更高的代谢综合征风险。胎儿骨骼肌对母体营养限制特别敏感，这会损害肌肉质量和新陈代谢。对绵羊从妊娠日 (GD) 35 到 GD 135 进行 50% 营养限制治疗，我们常规观察营养限制 (NR) 组内胎儿体重的光谱表型。因此，我们的目的是评估母体 NR 对肌肉质量、肌纤维肥大、肌核点以及蛋白质合成和降解分子标记的影响，同时考虑到观察到的胎儿体重变化。在 NR 组中，我们将上四分位胎儿分为 NR(Non-SGA) (n = 11)，将下四分位胎儿分为 NR(SGA) (n = 11)。对照组 (n = 12) 在整个怀孕期间获得 100% 的营养需求。在 GD 135 时，收集胎儿血浆和器官，并对腓肠肌和比目鱼肌取样进行研究。结果显示，与 NR（非 SGA）和对照相比，NR（SGA）胎儿的绝对组织/器官重量（包括比目鱼肌和腓肠肌）降低（ P < 0.05）。与对照组相比，NR(SGA) 腓肠肌 ( P = 0.0092) 和比目鱼肌 ( P = 0.0097) 的肌纤维横截面积更小。在腓肠肌内，与对照组相比，NR(SGA) 中每根肌纤维的肌核数量减少 ( P = 0.0442)。皮质醇可能会诱导蛋白质降解。然而，各组之间的胎儿皮质醇没有差异。然而，对于腓肠肌，皮质醇受体（ NR3C1；P = 0.0124）和FOXO1 （ P = 0。0131) 与对照组相比，NR(SGA) 中的表达上调，而 NR(Non-SGA) 与其他两组没有差异。 KLF15在 NR(SGA) 和 NR(Non-SGA) 中均上调 ( P = 0.0002)；而FBXO32 、 TRIM63 、 BCAT2或MSTN没有差异。对于比目鱼肌，与对照相比，NR（SGA）中KLF15 mRNA上调（ P =0.0145），与对照相比，NR（SGA）和NR（Non-SGA）中MSTN表达增加（ P =0.0259）。在蛋白质水平上，所提到的分子和总泛素标记蛋白质在各组之间均没有差异（ P > 0.05）。各组肌肉的蛋白质合成指标（总 MTOR 和磷酸化 MTOR、EI4EBP1 和 RPS6KB1）没有差异（ P > 0.05）。总的来说，结果强调母体 NR 对 NR(SGA) 和 NR(Non-SGA) 胎儿肌肉质量的影响不同，肌纤维横截面积和肌核数量的变化部分解释了这些差异。