Transcriptional response of skeletal muscle to a low-protein gestation diet in porcine offspring accumulates in growth- and cell cycle-regulating pathways

Abstract

Inadequate maternal protein supply during gestation represents an environmental factor that affects physiological signaling pathways with long-term consequences for growth, function, and structure of various tissues. Hypothesizing that the offspring's transcriptome is persistently altered by maternal diets, we used a porcine model to monitor the longitudinal expression changes in muscle to identify pathways relevant to fetal initiation of postnatal growth and development. German Landrace gilts were fed isoenergetic gestational diets containing 6.5% (LP) or 12.1% protein. The longissimus dorsi samples were collected from offspring at 94 days postconception (dpc) and 1, 28, and 188 days postnatum (dpn) for expression profiling. At 94 dpc, 1 dpn, and 28 dpn relatively few transcripts (<130) showed an altered abundance between the dietary groups. In fact, at 94 dpc genes of G2/M checkpoint regulation and mitotic roles of Polo-like kinases showed lowered transcript abundance in LP. At 188 dpn 677 transcripts were altered including those related to oxidative phosphorylation, citrate cycle, fatty acid metabolism (higher abundance in LP) and cell cycle regulation (lower abundance in LP). Correspondingly, transcriptional alterations during pre and postnatal development differed considerably among dietary groups, particularly for genes related to cell cycle regulation (G1/S and G2/M checkpoint regulation; cyclines), growth factor signaling (GH, IGF1, mTOR, RAN, VEGF, INSR), lipid metabolism, energy metabolism, and nucleic acid metabolism. In skeletal muscle, fetal programming related to maternal LP diets disturbed gene expression in growth-related pathways into adulthood. Diet-dependent gene expression may hamper proper development, thereby affecting signaling pathways related to energy utilization.

Transcriptome analysis of porcine M. semimembranosus divergent in intramuscular fat as a consequence of dietary protein restriction

“…fatty acid metabolism, were commonly differentially expressed in all three studies. Our phenotypic and gene expression findings in relation to dietary restriction at the post natal stage show interesting parallels with the impact of restricted protein at the gestational stage [59]. Restriction of growth performance was observed in the pigs restricted in protein during gestation as in those of the present study, which were restricted in protein in their own diets.…”

“…Da Costa et al [15] examined energy and protein restriction and applied a small muscle specific microarray to male Duroc pigs on restricted and adequate energy and protein. Oster et al [59] applied a reduced protein supply to the maternal diet during gestation; subsequently measuring phenotype and transcription in the offspring at different stages post mortem using the same array platform as employed in the present study. Da Costa et al [15] in common with the present study, found reduced growth performance and increased IMF accumulation in pigs on restricted protein and energy diets.…”

“…Offspring offered poor protein supply during gestation had significantly lower body weight and lowered transcriptional abundance of growth-related genes and pathways at day 1 post natal. They compensated in terms of weight when offered adequate protein in later growth stages, but this was driven by fat accumulation while myofibrillar numbers remained low [59]. Despite reduced lean growth performance it was noteworthy however that major transcriptional differences as a result of protein restriction in gestation were not evident until approximately 188 days post natal.…”

Application of the microarray technology to the transcriptional analysis of muscle phenotypes in pigs

“…It can be inferred from these results that SCD might be an interesting candidate biomarker for IMF accumulation in swine. In contrast, most differences in muscle gene expression are evidenced in the long term when sows are exposed to lowprotein diets (Oster et al 2012b). Feeding pregnant sows with either high-and low-protein diets has short-and long-term consequences on the muscle gene expression profile of their offspring.…”

Folate Deficiency during Early-Mid Pregnancy Affects the Skeletal Muscle Transcriptome of Piglets from a Reciprocal Cross

“…Microarrays have been used to investigate differential gene expression in pigs of different breeds and developmental stages at the transcriptome level, and have proved to be a powerful and direct tool for the study of known transcripts in complex developmental programs [26-28]. In this study, using the 4 × 44K Agilent porcine oligo microarray, we investigated the effects of folate deficiency during early-mid pregnancy on the skeletal muscle transcriptome of piglets from a reciprocal cross.…”