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Background Reproductive development may be advanced in bull calves through enhanced dietary intake during the early life period. This effect between enhanced nutrition with subsequent earlier reproductive development is orchestrated through signalling within the hypothalamic-pituitary-testicular axis. Within the hypothalamus, the arcuate nucleus (ARC) is crucial for the integration of peripheral metabolic status with subsequent gonadotropin releasing hormone (GnRH) signalling; however, the precise molecular control regulating this effect is not fully known. The aim of this study was to evaluate the global transcriptomic and proteomic responses to varied plane of nutrition during early calf-hood in young dairy bull calves. Additionally, we sought to integrate these ‘omics’ datasets to determine key genes and proteins contributing to earlier reproductive development. Between 2–12 weeks of age, 30 Holstein-Friesian bull calves (mean age: 17.5 days; mean bodyweight 48.8 kg), were offered either a high or moderate plane of nutrition with 15 calves in each group. At 12 weeks of age, all calves were euthanised and the ARC tissue isolated from each calf. The ARC tissue was then used for global transcriptomic (miRNAseq and mRNAseq) and proteomic analyses. Results Bioinformatic analyses were undertaken to determine differentially expressed transcripts (FDR < 0.1; fold change > 1.5) between the dietary treatment groups, resulting in the identification of 1 differentially expressed miRNA (miR-2419-3p) and 83 differentially expressed mRNA in the ARC region. mRNA target gene prediction identified Complement 3 ( C3 ) as a target of miR-2419-3p, suggesting a relationship between the two transcripts. Furthermore, through a co-regulatory network analysis conducted on the proteomics dataset, C3 was revealed as a hub protein. Additionally, through the proteomic network analysis, C3 was interacting with proteins involved in both insulin and GnRH signalling, highlighting a potential role for C3 in mediated the effect of enhanced nutritional status with earlier reproductive development within the ARC. Conclusion This study highlights an effect of altered plane of nutrition in early life on the molecular control of the hypothalamic ARC. Additionally, results generated suggest a potential role for the C3 gene in mediating the interaction between enhanced metabolic status with reproductive development within the ARC, regulated by miR-2419-3p.

The genetic mechanisms controlling residual feed intake (RFI) in beef cattle are still largely unknown. Here we performed whole transcriptome analyses to identify differentially expressed (DE) genes and their functional roles in liver tissues between six extreme high and six extreme low RFI steers from three beef breed populations including Angus, Charolais, and Kinsella Composite (KC). On average, the next generation sequencing yielded 34 million single-end reads per sample, of which 87% were uniquely mapped to the bovine reference genome. At false discovery rate (FDR) < 0.05 and fold change (FC) > 2, 72, 41, and 175 DE genes were identified in Angus, Charolais, and KC, respectively. Most of the DE genes were breed-specific, while five genes including TP53INP1 , LURAP1L , SCD , LPIN1 , and ENSBTAG00000047029 were common across the three breeds, with TP53INP1 , LURAP1L , SCD , and LPIN1 being downregulated in low RFI steers of all three breeds. The DE genes are mainly involved in lipid, amino acid and carbohydrate metabolism, energy production, molecular transport, small molecule biochemistry, cellular development, and cell death and survival. Furthermore, our differential gene expression results suggest reduced hepatic lipid synthesis and accumulation processes in more feed efficient beef cattle of all three studied breeds.

Enhanced early-life nutrition in calves holds potential for improving economically important traits, including growth rate, milk yield and reproductive development. However, the mechanisms through which these nutritional strategies affect skeletal muscle development remain to be fully elucidated. This study aimed to evaluate the impact of enhanced dietary intake during early calf-hood on the transcriptional profile of skeletal muscle tissue. Angus × Holstein-Friesian heifer dairy-calves were offered either a high (HI, n  = 10) or moderate (MOD, n  = 10) diet from 3 to 21 weeks of life. At 21 weeks of age, M. longissimus thoracis et lumborum tissue was harvested from all calves and subsequently subjected to mRNA sequencing. Altered early-life nutrition led to the differential expression of 482 genes in the skeletal muscle transcriptome (False discovery rate (FDR) < 0.1; fold change > 1.5) between HI and MOD calves. Differentially expressed genes were involved in processes related to metabolism, energy production and cellular growth and proliferation and included enrichment of the Sirtuin signalling pathway and skeletal muscle system development and function. The results of this study identify novel gene transcripts involved in the molecular regulation of skeletal muscle response to nutritional modulation, offering insights into muscle development and its potential impact on tissue composition.

Background Enhanced nutrition during the early calfhood period has been shown to lead to earlier pubertal development in heifer calves. This is of interest as earlier pubertal onset can subsequently facilitate earlier calving which can economically benefit production systems. Reproductive development in heifers is regulated by the hypothalamic-pituitary-ovarian signalling pathway. In particular the anterior pituitary gland is central to reproductive development, through the dynamics of gonadotropic pulsatility. However, despite clear knowledge of the influence of enhanced dietary intake on subsequent reproductive development, the molecular control governing this response in the pituitary gland within the hypothalamic-pituitary-ovarian signalling axis in heifer calves is not fully understood. The objective of this study was to examine the effect of an enhanced plane of nutrition during early life on the anterior pituitary gland of heifer calves through both transcriptomic and proteomic analyses. Between 3 and 21 weeks of age, heifer calves were offered either a high (HI, n  = 14) or moderate (MOD, n  = 14) plane of nutrition, designed to elicit target growth rates of 1.2 and 0.5 kg/d for HI and MOD groups, respectively. All calves were euthanised at 21 weeks of age and anterior pituitary tissue harvested for subsequent use in global transcriptomic and proteomic analyses. Results Average daily gain was affected by diet ( P  < 0.001) and was 1.18 and 0.50 kg/day, for HI and MOD calves, respectively. RNAseq analysis resulted in the identification of 195 differentially expressed genes (P adj <0.05; fold change > 1.5), with 277 proteins identified as differentially abundant (P adj <0.05; fold change > 1.5) between contrasting dietary treatment groups. Biochemical pathway analysis of differentially affected genes and proteins revealed an enrichment for both growth hormone and GnRH signalling pathways (P adj .<0.05). Additionally, pathway analysis predicted an effect of enhanced dietary intake on endocrine function within the anterior pituitary gland as well as on reproductive system development and function (P adj .<0.05). Conclusions Results from this study show that an enhanced dietary intake during early calfhood affected the molecular control of the anterior pituitary gland in heifer calves in early life.

Enhanced early life nutrition accelerates sexual development in the bull calf through neuroendocrine-signalling mediated via the hypothalamic–pituitary–testicular axis. Our aim was to assess the impact of contrasting feeding regimes in bull calves during the first 12 weeks of life on the testes transcriptome and proteome. Holstein–Friesian bull calves were offered either a high (HI) or moderate (MOD) plane of nutrition, designed to support target growth rates of 1.0 and 0.5 kg/day, respectively. At 12 weeks of age all calves were euthanized, testicular parenchyma sampled, and global transcriptome (miRNAseq and mRNAseq) and proteome analyses undertaken. Bioinformatic analyses revealed 7 differentially expressed (DE) miRNA and 20 DE mRNA. There were no differentially abundant proteins between the two dietary groups. Integration of omics results highlighted a potential role for the cadherin gene, CDH13 , in earlier reproductive development. Furthermore, co-regulatory network analysis of the proteomic data revealed CDH13 as a hub protein within a network enriched for processes related to insulin, IGF-1, androgen and Sertoli cell junction signalling pathways as well as cholesterol biosynthesis. Overall, results highlight a potential role for CDH13 in mediating earlier reproductive development as a consequence of enhanced early life nutrition in the bull calf.

Identifying and breeding cattle that are more feed efficient is of great benefit to beef production. Additionally, it is crucial that genes contributing to feed efficiency are robust across varying management settings including dietary source as well as being relevant across contrasting breeds of cattle. The aim of this study was to determine miRNAs that are contributing to the expression of residual feed intake (RFI) across two breeds and dietary sources. miRNA profiling was undertaken in Longissimus dorsi tissue of Charolais and Holstein–Friesian steers divergent for RFI phenotype following two contrasting consecutive diets (high-forage and high-concentrate). Ten miRNA were identified as differentially expressed (adj. P < 0.1) across the breed and diet contrasts examined. Of particular interest was the differential expression of miR-2419-5p and miR-2415-3p, both of which were up-regulated in the Low-RFI Charolais steers across each dietary phase. Pathway analysis of target mRNA genes of differentially expressed miRNA revealed enrichment (P < 0.05) for pathways including metabolic related pathways, insulin receptor signalling, adipogenesis as well as pathways related to skeletal muscle growth. These results provide insight into the skeletal muscle miRNAome of beef cattle and their potential molecular regulatory mechanisms relating to feed efficiency in beef cattle.

Adipose tissue represents not only an important energy storage tissue but also a major endocrine organ within the body, influencing many biochemical systems including metabolic status, immune function and energy homeostasis. The objective of this study was to evaluate the effect of an enhanced dietary intake during the early calfhood period on the transcriptome of visceral adipose tissue. Artificially reared Angus × Holstein–Friesian heifer calves were offered either a high (HI, n = 15) or moderate (MOD, n = 15) plane of nutrition from 3 to 21 weeks of life. At 21 weeks of age all calves were euthanized, visceral adipose harvested and samples subsequently subjected to mRNA sequencing. Plane of nutrition resulted in the differential expression of 1214 genes within visceral adipose tissue (adj. p  < 0.05; fold change > 1.5). Differentially expressed genes were involved in processes related to metabolism and energy production. Biochemical pathways including Sirtuin signalling (adj. p  < 0.0001) and the adipogenesis pathways (adj. p  = 0.009) were also significantly enriched, indicating greater metabolic processing and adipogenesis in the calves on the high plane of nutrition. Results from this study identify novel genes regulating the molecular response of visceral adipose tissue to an improved plane of nutrition during early calfhood.

Background Provision of feed is a major determinant of overall profitability in beef production systems, accounting for up to 75% of the variable costs. Thus, improving cattle feed efficiency, by way of determining the underlying genomic control and subsequently selecting for feed efficient cattle, provides a method through which feed input costs may be reduced. The objective of this study was to undertake gene co-expression network analysis using RNA-Sequence data generated from Longissimus dorsi and liver tissue samples collected from steers of two contrasting breeds (Charolais and Holstein-Friesian) divergent for residual feed intake (RFI), across two consecutive distinct dietary phases (zero-grazed grass and high-concentrate). Categories including differentially expressed genes (DEGs) based on the contrasts of RFI phenotype, breed and dietary source, as well as key transcription factors and proteins secreted in plasma were utilised as nodes of the gene co-expression network. Results Of the 2,929 DEGs within the network analysis, 1,604 were reported to have statistically significant correlations ( ≥  0.80), resulting in a total of 43,876 significant connections between genes. Pathway analysis of clusters of co-expressed genes revealed enrichment of processes related to lipid metabolism (fatty acid biosynthesis, fatty acid β-oxidation, cholesterol biosynthesis), immune function, (complement cascade, coagulation system, acute phase response signalling), and energy production (oxidative phosphorylation, mitochondrial L-carnitine shuttle pathway) based on genes related to RFI, breed and dietary source contrasts. Conclusions Although similar biological processes were evident across the three factors examined, no one gene node was evident across RFI, breed and diet contrasts in both liver and muscle tissues. However within the liver tissue, the IRX4 , NR1H3 , HOXA13 and ZNF648 gene nodes, which all encode transcription factors displayed significant connections across the RFI, diet and breed comparisons, indicating a role for these transcription factors towards the RFI phenotype irrespective of diet and breed. Moreover, the NR1H3 gene encodes a protein secreted into plasma from the hepatocytes of the liver, highlighting the potential for this gene to be explored as a robust biomarker for the RFI trait in beef cattle.

Periodic feed restriction is used in cattle production to reduce feed costs. When normal feed levels are resumed, cattle catch up to a normal weight by an acceleration of normal growth rate, known as compensatory growth, which is not yet fully understood. Illumina Miseq Phylogenetic marker amplicon sequencing of DNA extracted from rumen contents of 55 bulls showed that restriction of feed (70% concentrate, 30% grass silage) for 125 days, to levels that caused a 60% reduction of growth rate, resulted in a large increase of relative abundance of Methanobrevibacter gottschalkii clade (designated as OTU-M7), and a large reduction of an uncharacterised Succinivibrionaceae species (designated as OTU-S3004). There was a strong negative Spearman correlation (ρ = -0.72, P = <1x10(-20)) between relative abundances of OTU-3004 and OTU-M7 in the liquid rumen fraction. There was also a significant increase in acetate:propionate ratio (A:P) in feed restricted animals that showed a negative Spearman correlation (ρ = -0.69, P = <1x10(-20)) with the relative abundance of OTU-S3004 in the rumen liquid fraction but not the solid fraction, and a strong positive Spearman correlation with OTU-M7 in the rumen liquid (ρ = 0.74, P = <1x10(-20)) and solid (ρ = 0.69, P = <1x10(-20)) fractions. Reduced A:P ratios in the rumen are associated with increased feed efficiency and reduced production of methane which has a global warming potential (GWP 100 years) of 28. Succinivibrionaceae growth in the rumen was previously suggested to reduce methane emissions as some members of this family utilise hydrogen, which is also utilised by methanogens for methanogenesis, to generate succinate which is converted to propionate. Relative abundance of OTU-S3004 showed a positive Spearman correlation with propionate (ρ = 0.41, P = <0.01) but not acetate in the liquid rumen fraction.

The selection of cattle with enhanced feed efficiency is of importance with regard to reducing feed costs in the beef industry. Global transcriptome profiling was undertaken on liver and skeletal muscle biopsies from Simmental heifers and bulls divergent for residual feed intake (RFI), a widely acknowledged feed efficiency phenotype, in order to identify genes that may be associated with this trait. We identified 5 genes (adj. p < 0.1) to be differentially expressed in skeletal muscle between high and low RFI heifers with all transcripts involved in oxidative phosphorylation and mitochondrial homeostasis. A total of 11 genes (adj. p < 0. 1) were differentially expressed in liver tissue between high and low RFI bulls with differentially expressed genes related to amino and nucleotide metabolism as well as endoplasmic reticulum protein processing. No genes were identified as differentially expressed in either heifer liver or bull muscle analyses. Results from this study show that the molecular control of RFI in young cattle is modified according to gender, which may be attributable to differences in physiological maturity between heifers and bulls of the same age. Despite this we have highlighted a number of genes that may hold potential as molecular biomarkers for RFI cattle.