The molecular control of the hypothalamic-pituitary-testicular axis in the bull

The objectives of this thesis were: 1) to understand the effect of early calf nutrition on the transcriptome of subcutaneous adipose tissue and their downstream effects on the hypothalamic-pituitary-testicular (HPT) axis in Holstein Friesian bulls, 2) to characterise the physiological, cellular and transcriptional response of the HPT to contrasting planes of nutrition during early calf-hood in Holstein Friesian bulls and 3) to describe key pathways in the HPT axis which are under nutritional control. Holstein Friesian bull calves with a mean (±S.D.) age and bodyweight of 19 (±8.2) days and 47.5 (±5.3) kg, respectively, were assigned to either a high (n=10) or low (n=10) plane of nutrition. Diets were designed in order to achieve a growth rate of 1.2 and 0.5 kg/day for the high and low planes of nutrition, respectively. At 126±1.1 days of age, the calves were euthanized. In the first study, animal performance and systemic concentrations of metabolic hormones and metabolites were measured. Testicular histology, targeted gene and protein expression of the arcuate nucleus, anterior pituitary and testes were also measured. Testes from adult bulls that were reared under similar conditions were also excised for gene expression comparison. The metabolites and metabolic hormones generally reflected the improved metabolic status of the calves on the high plane of nutrition (P<0.001). Only ghrelin receptor was upregulated in the anterior pituitary (P<0.05) and ARC (P<0.10) in the low plane of nutrition compared to high plane of nutrition. Calves offered a high plane of nutrition were heavier at slaughter, had larger testes, larger seminiferous tubule diameter, more mature spermatogenic cells and more Sertoli cells in accordance with both morphological and transcriptional data. This study suggests that a high plane of nutrition during the early calf-hood period alters gene expression within the HPT and testicular morphology which hastens spermatogenesis and testicular development. In the second study, arcuate nucleus from the hypothalamus, anterior pituitary and testes samples were harvested and RNASeq analysis was performed. There were 0, 49 and 1,346 genes differentially expressed in the arcuate nucleus, anterior pituitary and testicular tissue of bulls on the low relative to the high plane of nutrition, respectively (P<0.05; False Discovery Rate<0.05). Plane of nutrition had no effect on gene expression in the arcuate nucleus or anterior pituitary tissue with regard to the early onset of puberty. Low plane of nutrition down regulated the expression of genes involved in cholesterol and androgen biosynthesis in the testes. A low plane of nutrition also resulted in up-regulation of genes known to positively influence male fertility and formation of gonadal cells. This study aids in the detection of molecular based biomarkers for the selection of cattle with early pubertal onset. In the third study, subcutaneous adipose tissue samples were harvested and RNASeq analysis was performed. There were 674 genes differentially expressed in adipose tissue of calves on the low compared with the high plane of nutrition (P<0.05; FDR<0.05; fold change >2.0). Plane of nutrition altered the expression of genes across an array of putative biological processes but the most dominant cellular processes affected were cellular energy production and branched chain amino acid degradation. A high plane of nutrition caused upregulation of genes such as leptin (LEP) and adiponectin (ADIPOQ), which are known to directly affect reproductive function. These results provide an insight into the effect of augmenting the plane of nutrition of Holstein-Friesian bull calves in the prepubertal period on the transcriptome of adipose tissue.