Enhanced early-life nutrition upregulates cholesterol biosynthetic gene expression and Sertoli cell maturation in testes of pre-pubertal Holstein bulls.

Well-fed prepuberal Holstein bulls had larger testes, earlier puberty, higher LH, testosterone and IGF-1, earlier and more proliferating and differentiating Sertoli cells, and greater sperm production potential. The objective was to determine effects of pre-pubertal nutrition on mRNA expression of testicular genes. Holstein bull calves were fed high or low diets (20 or 12% crude protein, respectively and 71.6 or 64.4% Total Digestible Nutrients) from 2 wk, castrated at 8, 16, 24 and 32 wk and testicular mRNA extracted and sequenced. Differential expression of genes mainly occurred at 16 and 24 wk. At 16 wk, functional analysis (DAVID) of DE mRNA revealed common biological processes including "cholesterol" and "fatty acid biosynthesis," with most genes (including HMGCR, HMGCS1, HSD17) upregulated in high-diet bulls (P < 0.05). Major pathways enriched at 16 wk were "cholesterol biosynthesis", "steroid metabolism" and "activation of gene expression by Sterol regulatory element binding protein (SREBP)" (P < 0.05). In high-diet bulls, mature Sertoli cell marker Connexin 43, was upregulated at 16 wk and immature Sertoli cell marker (AMH) downregulated at 24 wk. There was an indirect interaction between insulin family receptor and most upregulated cholesterol biosynthesis genes. Pre-pubertal nutrition enhanced testicular cholesterol/steroid biosynthesis and Sertoli cell maturation.