GSE125082
Enhanced early-life nutrition upregulates cholesterol biosynthetic gene expression and Sertoli cell maturation in testes of pre-pubertal Holstein bulls
Pre-pubertal Holstein bull calves fed a higher plane of nutrition had larger testes, earlier puberty, higher serum LH, testosterone and greater sperm production potential than those fed a restricted diet. In addition, pre-pubertal calves fed a high-nutrition diet had higher IGF-I and more proliferating and differentiating Sertoli cells much earlier in life, compared to those fed normal or low-nutrition diets. The objective was to determine changes in mRNA expression of genes in the testes of bulls fed either a high or low pre-pubertal diet.  Holstein bull calves maintained on either a high (20% crude protein (CP) and 71.6% Total Digestible Nutrients (TDN)) or low (12% CP and 64.4% TDN) diet from 2 wk of age, were 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, with minor changes detected at 32 wk. At 16 wks, functional analysis of DE mRNA with DAVID revealed the common biological processes enriched to be "cholesterol" and "fatty acid biosynthesis" with majority of the genes including HMGCR, HMGCS1, HSD17 being upregulated in high-diet bulls (P<0.05). Major pathways enriched at 16 wks were "cholesterol biosynthesis", "steroid metabolism" and "activation of gene expression by Sterol regulatory element-binding protein (SREBP)" (P<0.05). Mature Sertoli cell marker Connexin 43, was upregulated at 16 wk, whereas an immature Sertoli cell marker, AMH was downregulated at 24 wk, in the high-diet group. Network analysis using IPA, revealed an indirect interaction between insulin family receptor and most upregulated cholesterol biosynthesis genes, implying regulation of testicular function. Thus, enhanced pre-pubertal nutrition in Holstein bulls enhanced testicular cholesterol/steroid biosynthesis and Sertoli cell maturation to promote early reproductive development. Overall design: Holstein bull calves (n=28) maintained on either a high or low diet from 2 wk of age, were castrated at 8, 16, 24 and 32 wk and testicular mRNA extracted and sequenced.