Maternal nutrient restriction in mid-to-late gestation influences fetal mRNA expression in muscle tissues in beef cattle
Citation
Paradis, F., Wood, K.M., Swanson, K.C., Miller, S.P., McBride, B.W., Fitzsimmons, C. (2017). Maternal nutrient restriction in mid-to-late gestation influences fetal mRNA expression in muscle tissues in beef cattle. BMC Genomics, [online] 18(1), http://dx.doi.org/10.1186/s12864-017-4051-5
Plain language summary
In this study, pregnant cows were fed either a restricted diet of 85% of energy requirements or a diet of 140% of energy requirements during mid-to-late-gestation in order to determine its effect on the development of the fetus and the expression of genes involved in growth as well as muscle and fat formation. The results indicate that the nutrient restriction impacted maternal weight, however no differences were found in the weight or size measurements of the fetuses. Restricted fetal calves had increased gene expression for multiple genes in a back muscle called longissimus dorsi (LD) but no significant differences were found in a leg muscle called semitendinosus (ST) muscle. Feed restriction had a greater impact on the methylation level of the Differentially Methylated Region 2 (DMR2) of IGF2, a growth-promoting gene, in LD muscle as compared to ST muscle between treatment groups. A negative correlation existed between IGF2 expression and IGF2 DMR2 methylation level in both LD and ST muscles. The data suggests that nutrient restriction during mid-to-late of gestation can alter the expression of genes involved in growth as well as muscle and fat formation in fetal muscle without apparent differences in observable fetal characteristics such as weight. It also appears that the impact of feed restriction varies between muscles suggesting a priority for nutrient partitioning depending on the function and/or the composition of the muscle.
Abstract
Background: Manipulating maternal nutrition during specific periods of gestation can result in re-programming of fetal and post-natal development. In this experiment we investigated how a feed restriction of 85% compared with 140% of total metabolizable energy requirements, fed to cows during mid-to-late gestation, influences phenotypic development of fetuses and mRNA expression of growth (Insulin-Like Growth Factor family and Insulin Receptor (INSR)), myogenic (Myogenic Differentiation 1 (MYOD1), Myogenin (MYOG), Myocyte Enhancer Factor 2A (MEF2A), Serum Response Factor (SRF)) and adipogenic (Peroxisome Proliferator Activated Receptor Gamma (PPARG)) genes in fetal longissimus dorsi (LD) and semitendinosus (ST) muscle. DNA methylation of imprinted genes, Insulin Like Growth Factor 2 (IGF2) and Insulin Like Growth Factor 2 Receptor (IGF2R), and micro RNA (miRNA) expression, were also examined as potential consequences of poor maternal nutrition, but also potential regulators of altered gene expression patterns. Results: While the nutrient restriction impacted dam body weight, no differences were observed in phenotypic fetal measurements (weight, crown-rump length, or thorax circumference). Interestingly, LD and ST muscles responded differently to the differential pre-natal nutrient levels. While LD muscle of restricted fetal calves had greater mRNA abundances for Insulin Like Growth Factor 1 and its receptor (IGF1 and IGF1R), IGF2R, INSR, MYOD1, MYOG, and PPARG, no significant differences were observed for gene expression in ST muscle. Similarly, feed restriction had a greater impact on the methylation level of IGF2 Differentially Methylated Region 2 (DMR2) in LD muscle as compared to ST muscle between treatment groups. A negative correlation existed between IGF2 mRNA expression and IGF2 DMR2 methylation level in both LD and ST muscles. Differential expression of miRNAs 1 and 133a were also detected in LD muscle. Conclusions: Our data suggests that a nutrient restriction of 85% as compared to 140% of total metabolizable energy requirements during the 2nd half of gestation can alter the expression of growth, myogenic and adipogenic genes in fetal muscle without apparent differences in fetal phenotype. It also appears that the impact of feed restriction varies between muscles suggesting a priority for nutrient partitioning depending on muscle function and/or fiber composition. Differences in the methylation level in IGF2, a well-known imprinted gene, as well as differences in miRNA expression, may be functional mechanisms that precede the differences in gene expression observed, and could lead to trans-generational epigenetic programming.