ABSTRACT Maternal undernutrition during late gestation causes intrauterine growth restriction (IUGR), affecting skeletal muscle development and increasing the risk of metabolic disorders in offspring. This study investigated the effects of maternal undernutrition on muscle growth, metabolism, and transcriptomic regulation in sheep fetuses. We used a sheep IUGR model, where maternal nutrition was restricted from gestation Day 90–130. The sheep were divided into control (0.63 MJ ME·BW −0 · 75 ·day −1 ) and undernutrition (MU1: 0.33, MU2: 0.20 MJ ME·BW −0 · 75 ·day −1 ) groups. Maternal undernutrition reduced fetal longissimus thoracis et lumborum (LTL) weight, protein and fat content, and muscle fiber cross‐sectional area ( p < 0.05). The MU groups exhibited an increased proportion of cells in the G0/G1 phase and a reduced proliferation index ( p < 0.05). In the MU2 group, myogenic regulators ( Pax7 , MYF5 , and MSTN ) were upregulated ( p < 0.05), and fiber composition shifted toward glycolytic phenotypes, with decreased MyHC I and increased MyHC IIA expression ( p < 0.05). Glucose‐6‐phosphate, glycogen, and the essential and non‐essential amino acids (Leu and Ala) were elevated, and lactate and triglyceride levels were reduced ( p < 0.05) in the MU2 group. The MU2 group exhibited reduced mitochondrial complex I ( p < 0.05) and III activity ( p < 0.01), mitochondrial DNA depletion ( p < 0.01), decreased citrate synthase activity ( p < 0.05), and increased creatine kinase activity ( p < 0.01). The MU2 group showed higher expression of the endoplasmic reticulum stress‐related genes PERK , ERDj , CHOP , and FIP200 ( p < 0.05), as well as ATF6B , XBP1 , and P62 ( p < 0.01). Transcriptomic analysis revealed enrichment in pathways related to myosin complexes, cell growth, mitochondrial energy metabolism regulation, and ribosomal pathways. Our findings suggest that maternal undernutrition during late gestation may disrupt myogenesis and alter fiber type composition, coinciding with potential mitochondrial dysfunction, ER stress, and transcriptional shifts in ribosomal pathways.
Qiao et al. (Fri,) studied this question.