526 Late-Breaking: Poor Maternal Diet Alters the Muscle Proteome at Mid-gestation in Sheep

Abstract

Abstract Maternal diet during gestation can negatively impact fetal development and postnatal growth and body composition. We hypothesized that poor maternal nutrition during gestation would alter protein expression in muscle at day 90 of gestation in sheep. Pregnant ewes (n = 24) were fed a control, restricted, or over-fed diet (100, 60, or 140% of NRC requirements for total digestible nutrients, respectively; n = 8 per treatment) starting at day 30 of gestation. At day 90 of gestation, fetal longissimus dorsi samples were collected (CON, RES, and OVER, respectively). Sarcoplasmic proteins were trypsin digested and subjected to multiplexed, label-based quantitative mass spectrometry analysis integrating Tandem Mass Tags. Differential expression of proteins was identified via two statistical techniques: ANOVA followed by Tukey’s HSD post-hoc tests, and regularized regression via 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. Within these pathways, 26S proteasome non-ATPase regulatory subunit (PSMD) 1, PSMD6, and PSMD14, components of the 26 S proteasome, were reduced 6 to 10% in OVER relative to CON offspring. Proteins involved in elongation and initiation, including eukaryotic initiation factor (EIF) 2 subunit 3, EIF 4 gamma 2, and EIF 3 subunit B were reduced 8 to 15% in OVER relative to CON offspring. Mitogen-activated protein kinase (MAPK) 1 and dual-specificity MAPK kinase (MEKK) 1 were increased by 12% in RES relative to OVER and CON offspring. Together, these data indicate that protein degradation and synthesis are altered in mid-gestation muscle development in OVER offspring, and that cell signaling related to cell proliferation is affected in RES offspring. These changes may contribute to the phenotypic and metabolic changes observed during fetal development and postnatal growth.