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

ABSTRACT: 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.

ORGANISM(S): Bos taurus

PROVIDER: GSE125082 | GEO | 2019/05/15

REPOSITORIES: GEO

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Project description:Background: To reduce costs of rearing replacement heifers, researchers have focused on decreasing age at breeding and first calving, and to increase returns upon initiation of lactation the focus has been on increasing mammary development prior to onset of first lactation. Enhanced plane of nutrition pre-weaning may benefit the entire replacement heifer operation by promoting mammary gland development and greater future production. Methods: Twelve Holstein heifer calves (<1 wk old) were reared on 1 of 2 dietary treatments (n = 6/group) for 8 wk: a control group fed a restricted milk replacer at 0.45 kg/d (R, 20% crude protein, 20% fat), or an accelerated group fed an enhanced milk replacer at 1.13 kg/d (EH, 28% crude protein, 25% fat). At weaning (8 wk), calves were euthanized and sub-samples of mammary parenchyma (PAR) and mammary fat pad (MFP) were harvested upon removal from the body. Total RNA from both tissues was extracted and sequenced using the Illumina HiSeq2500 platform. The Dynamic Impact Approach (DIA) and Ingenuity Pathway Analysis (IPA) were used for pathway analysis and functions, gene networks, and cross-talk analyses of the two tissues. Results: When comparing EH vs R 1,561 genes (↑895, and ↓666) and 970 genes (↑506, and ↓464) were found differentially expressed in PAR and MFP, respectively. DIA and IPA results highlight a greater proliferation and differentiation activity in both PAR and MFP, supported by an increased metabolic activity. When calves were fed EH, the PAR displayed transcriptional signs of greater overall organ development, with higher ductal growth and branching, together with a supportive blood vessel and nerve network. These activities were mediated by intracellular cascades, such as AKT, SHH, MAPKs, and Wnt, probably activated by hormones, growth factors, and endogenous molecules. The analysis also revealed strong communication between MFP and PAR, with the first enhancing the development of PAR through secreted growth factors and the recruitment of immune cells. Conclusion: The transcriptomics and bioinformatics approach highlighted the mechanisms that mediate the mammary gland response to a higher plane of nutrition in the pre-weaning period.

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

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