Moderate nutrient restriction of beef heifers alters expression of genes associated with tissue metabolism, accretion, and function in fetal liver, muscle, and cerebrum by day 50 of gestation

Authors: CROUSE, MATTHEW - North Dakota State University; CATON, JOEL - North Dakota State University; Cushman, Robert - Bob; MCLEAN, KYLE - University Of Kentucky; DAHLEN, CARL - North Dakota State University; BOROWICZ, PAWEL - North Dakota State University; REYNOLDS, LAWRENCE - North Dakota State University; WARD, ALISON - North Dakota State University

Submitted to: Translational Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/22/2019
Publication Date: 6/20/2019
Publication URL: https://handle.nal.usda.gov/10113/6480381
Citation: Crouse, M.S., Caton, J.S., Cushman, R.A., McLean, K.J., Dahlen, C.R., Borowicz, P.P., Reynolds, L.P., Ward, A.K. 2019. Moderate nutrient restriction of beef heifers alters expression of genes associated with tissue metabolism, accretion, and function in fetal liver, muscle, and cerebrum by day 50 of gestation. Translational Animal Science. 3(2):855-866. https://doi.org/10.1093/tas/txz026.
DOI: https://doi.org/10.1093/tas/txz026

Interpretive Summary: It has been proposed that maternal nutrient status during pregnancy can have life-long impacts on the physiology of the offspring by programming the function of the genome. We hypothesized that a moderate maternal nutrient restriction during the first 50 days of gestation in beef heifers would affect transcript abundance of genes impacting production efficiency phenotypes in fetal liver, muscle, and brain. Angus-cross heifers were estrus synchronized and assigned at breeding to 1 of 2 dietary treatments, Controls received 100% of nutrient requirements to gain a pound a day while the Restricted group received 60% of the Controls. At day 50 of pregnancy, Caesarian sections were performed, and fetal liver, muscle, and brain were collected. Abundance of gene products was determined and fit into functional categories associated with known impacts on production efficiencies. In the fetal liver, genes involved in metabolism were influenced by maternal nutrient status, while in fetal muscle genes involved in skeletal muscle development and embryonic development were influenced by maternal nutrient status. In the brain, genes involved in nerve development were influenced by maternal nutrient status, implying that behavior of the offspring may be developmentally programmed. This study is a first step toward demonstrating how the function of the genome may be developmentally programmed in fetal tissues based upon maternal nutrient intake during pregnancy. This suggests that factors that influence the nutrient intake of the cow during early pregnancy (e.g., drought) may impact the phenotype of the offspring by altering function of the genome. The exact mechanisms by which this occurs have yet to be identified. Identifying specific supplementation strategies to mitigate alterations in gene function due to aberrant maternal nutrition during early pregnancy will provide additional means to increase production efficiencies in beef cattle.

Technical Abstract: We hypothesized that a moderate maternal nutrient restriction during the first 50 d of gestation in beef heifers would affect transcript abundance of genes associated with tissue metabolism, accretion, and function in fetal liver, muscle, and cerebrum. Angus-cross heifers were estrus synchronized and assigned at breeding to one of two dietary treatments (CON- 100% of nutrient requirements to gain 0.45 kg/d; RES-60% of CON). At day 50 of gestation, 14 heifers were ovariohysterectomized, and fetal liver, muscle, and cerebrum were collected. Transcriptome analysis via RNA-seq was conducted on the Illumina HiSeq 2500 platform using 50-bp paired-end reads at a depth of 2 × 10.4M reads/sample. Bioinformatic analysis was performed using the Tuxedo Suite and ontological analysis with DAVID 6.8. For fetal liver, muscle, and cerebrum, a total of 548, 317, and 151 genes, respectively (P < 0.01) were differentially expressed, of which 201, 144, and 28 genes, respectively were false discovery rate protected (FDR; q < 0.10). Differentially expressed genes were screened for fit into functional categories of pathways or ontologies associated with known impacts on tissue metabolism, accretion, and function. In fetal liver, five functional categories of interest (n = 125 genes) were affected by nutritional treatment: metabolic pathways, protein kinase, nucleosome core, mRNA splicing, and complement/coagulation cascades, of which 105 genes were upregulated in RES. In fetal muscle, three functional categories of interest (n = 106 genes) were affected by nutritional treatment: skeletal muscle, embryogenesis, and signaling cascades, of which 64 genes were upregulated in RES. In fetal cerebrum, three functional categories of interest (n = 60 genes) were affected by nutritional treatment: hippocampus and neurogenesis, metal-binding, and cytoskeleton, of which 58 genes were upregulated in RES. These results demonstrate that a moderate maternal nutrient restriction during the first 50 d of gestation in beef heifers alters transcript abundance of genes potentially impacting tissue metabolism, accretion, and function in fetal liver, muscle, and cerebrum. Furthermore, these results indicate that affected categories are tissue-specific and moderate maternal nutrient restriction generally increases expression of genes in fetuses from RES fed dams. Finally, these data lay the foundation upon which further research that identifies phenotypic responses to changes in these pathways may be elucidated.