The objective of this study was to examine the effect of nutrition during the first 12 wk of life on aspects of the physiological and transcriptional regulation of testicular and overall sexual development in the bull calf. Holstein Friesian bull calves with a mean ±SD age and bodyweight of 17.5 (2.85) days and 48.8 (5.30) kg, respectively, were assigned to either a high (HI; n=15) or moderate (MOD; n=15) plane of nutrition and were individually fed milk replacer and concentrate to achieve overall target growth rates of at least 1.0 and 0.5 kg/day, respectively. Throughout the trial, animal growth performance, feed intake, and systemic concentrations of metabolites, metabolic and reproductive hormones were assessed. Additionally, pulsatility of reproductive hormones (luteinising hormone (LH), follicle stimulating hormone (FSH) and testosterone (TT) was recorded at 15 min intervals during a 10-h period at 10 wk of age. At 87 ± 2.14 days of age, all calves were euthanized, testes weighed, and testicular tissue harvested. Differential expression of messenger ribonucleic acid (mRNA) candidate genes involved in testicular development was examined using quantitative polymerase chain reaction (qPCR) assays. All data were analysed using the MIXED procedure in Statistical Analysis System (SAS) using terms for treatment as well as time for repeated measures. Blood metabolites and metabolic hormones generally reflected the improved metabolic status of the calves on the high plane of nutrition though the concentrations of reproductive hormones were not affected by diet. Calves offered HI had greater mean (SED) slaughter weight (112.4 v 87.70 (2.98) kg; P < 0.0001) and testicular tissue weight [29.2 v 20.1 (2.21) g; P = 0.0003], than MOD. Relative mRNA abundance data indicated advanced testicular development through up-regulation of genes involved in cellular metabolism (SIRT1; P = 0.0282), cholesterol biosynthesis (EBP; P = 0.007), testicular function (INSL3; P = 0.0077) and Sertoli cell development (CLDN11; P = 0.0054) in HI compared with MOD calves. In conclusion, results demonstrate that offering dairy bred male calves a high plane of nutrition during the first three months of life not only improves growth performance and metabolic status, but also advances testicular development consistent with more precocious sexual maturation.
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.
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.
Enhanced plane of nutrition and metabolic status are known to progress sexual development in the bull calf. This is facilitated through neuroendocrine signaling in the hypothalamic-pituitary-testicular signaling axis. Improved nutrition may lead to early release of hypothalamic gonadotropin releasing hormone (GnRH) and the subsequent production of follicle stimulating luteinizing hormones in the anterior pituitary and ultimately development of the testes and sexual development. Nonetheless the precise molecular mechanisms leading to this effect are yet to be expounded. The purpose of this study was to evaluate differentially expressed (DE) genes within the testes of bull calves differentially fed for the first 12 weeks of life. The main functions of the testes are the biosynthesis of androgens by the leydig cells and sperm production by the seminiferous tubules. Accelerating the development of this tissue may lead to enhanced reproductive development at an earlier stage. Holstein Friesian bull calves with a mean (SEM) age and bodyweight of 17.5 (2.8) days and 48.8 (5.3) kg, respectively, were assigned to either a high (H; n = 15) or moderate (M; n = 15) plane of nutrition, to achieve an average target growth rate of 1.0 and 0.5 kg/day, respectively. Calves on H and M received 1.5 and 0.5 kg of milk replacer (MR) per day, reconstituted at 15 and 12.5% (w/v), respectively. Calves on H were offered concentrate ad libitum, while those on M received, 500g day-1. Both groups were offered 500 g of hay daily. At 87 days (±2.141) of age, all calves were euthanized and the testes recovered from all calves. RNA was isolated from all testes samples and subsequently subjected to RNAseq analysis. Calves offered a higher plane of nutrition were heavier at slaughter (112 v 88 kg, P < 0.001), reflective of their higher ADG (0.88 v 0.58 kg, P < 0.001). Similarly, H also had heavier testes (29.2 v 20.1 g, P < 0.05) compared to M calves. Results from RNAseq analysis identified 27 DE genes (p.adj< 0.1; fold change >1.5). Cholesterol biosynthesis was an enriched pathway and reproductive system development was also affected. We also saw that Claudin11 was an up regulated DE gene which is involved in sertoli cell development. The results from this study would advocate that there is potential effects of improved nutrition on reproductive function within the testes of bull calves at 12 weeks of age.
Improved nutrition and metabolic status during early life are known to advance sexual development in the bull calf. This is mediated through complex neuroendocrine signaling at the level of the hypothalamic-pituitary-testicular (HPT) axis resulting in precocious testicular development and spermatogenesis. The arcuate nucleus region (ARC) of the hypothalamus is centrally involved in the integration of peripheral metabolic cues with GnRH neuronal function and gonadotropin pulsatility which in turn stimulate testicular development. However, the precise molecular mechanisms regulating the influence of prevailing nutritional status on hypothalamic function are yet to be fully elucidated. The objective of this study was to evaluate differentially expressed genes (DEG) within the ARC of bull calves offered contrasting planes of nutrition during the first 12 weeks of life, to coincide with the characteristic transient gonadotropin rise. Holstein-Friesian bull calves with a mean (+SD) bodyweight and age of 48.8(5.3) kg and 17.5(2.8) days, respectively, were assigned to either a high energy (H; n = 15) or moderate energy (M; n = 15) plane of nutrition designed for growth rates of 1.0 and 0.5 kg/day, respectively. At 12 weeks of age all calves were euthanized and the ARC harvested. RNA was isolated from all ARC samples and RNAseq analysis conducted. As expected, H calves were heavier at euthanasia (H=112 kg; M=88 kg, P < 0.001). RNAseq analysis resulted in the identification of 83 DEG (P.adj< 0.1; fold change >1.5), all of which were down-regulated in H compared to M calves. DEG were enriched for biological pathways associated with immune function including complement system and acute phase response signaling (P.adj< 0.01). However, no DEG identified were directly involved in reproductive developmental processes. Results from this study suggest that the typically positive effect of enhanced nutrition on reproductive development may not be apparent within the ARC at 12 weeks of age.
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