Poor maternal diet during gestation alters offspring muscle proteome in sheep

The abundance of proteins related to protein synthesis and degradation, stress responses, metabolism, and oxidative stress are altered in the longissimus from offspring of poorly nourished dams. Poor maternal nutrition during gestation can result in reduced offspring muscle growth and altered muscle metabolism. We hypothesized that over- or restricted-nutrition during gestation would alter the longissimus dorsi muscle (LM) proteome of offspring. Pregnant ewes were fed 60% (restricted), 100% (control), or 140% (over) of National Research Council requirements for total digestible nutrients from day 30 of gestation until parturition. Fetal (RES, CON, OVER) LM were collected at days 90 and 135 of gestation, or from offspring within 24 h of birth. Sarcoplasmic proteins were isolated, trypsin digested, and subjected to multiplexed, label-based quantitative mass spectrometry analysis integrating tandem mass tag technology. Differential expression of proteins was identified by ANOVA followed by Tukey's HSD post hoc tests, and regularized regression via the elastic net. Significance was set at P < 0.05. Over-represented pathways containing differentially expressed proteins were identified by Reactome and included metabolism of proteins, immune system, cellular response to stress/external stimuli, developmental biology, and infectious disease. As a result of maternal diet, a total of 312 proteins were differentially expressed (day 90 = 89 proteins; day 135 = 115 proteins; birth = 131 proteins). Expression of eukaryotic initiation factor (EIF) 2S3, EIF3L, and EIF4G2 was lower in OVER fetuses at day 90 of gestation (P < 0.05). Calcineurin A and mitogen-activated protein kinase 1 were greater in RES fetuses at day 90 (P < 0.04). At day 135 of gestation, pyruvate kinase and lactate dehydrogenase A expression were greater in OVER fetuses than CON (P < 0.04). Thioredoxin expression was greater in RES fetuses relative to CON at day 135 (P = 0.05). At birth, proteins of the COP9 signalosome complex were greater in RES offspring relative to OVER (P < 0.05). Together, these data indicate that protein degradation and synthesis, metabolism, and oxidative stress are altered in a time and diet-specific manner, which may contribute to the phenotypic and metabolic changes observed during fetal development and postnatal growth. Lay Summary Poor maternal diet during gestation results in changes in body composition and metabolism in the offspring. Here, we demonstrate that over- and restricted-feeding during gestation alter global protein expression in the longissimus dorsi muscle of offspring during gestation and just after birth. These protein changes are related to protein synthesis and degradation, stress responses, metabolism, and oxidative stress. Proteins related to the initiation of protein translation were increased in offspring of over-fed dams at mid-gestation, while changes in abundance of enzymes associated with metabolism were altered in late gestation and just after birth. In offspring of restricted-fed ewes, proteins relating to cell signaling were increased at mid-gestation, while again, changes in late gestation and birth were related to metabolism, protein degradation, and stress responses. Together, these may provide a mechanism by which poor maternal diet during gestation alters the poor growth and development that occurs in these offspring.

Automated summary

Over- or restricted-nutrition during gestation alters the proteome of the longissimus dorsi muscle (LM) in offspring, affecting protein synthesis and degradation, stress responses, metabolism, and oxidative stress. These protein changes may contribute to the poor growth and development observed in the offspring.