Gene expression in bovine rumen epithelium during weaning indentifies molecular regulators of rumen development and growth

Authors: Connor, Erin; Baldwin, Ransom - Randy; Li, Congjun - Cj; Li, Robert; CHUNG, HOYUNG - National Institute Of Animal Science

Submitted to: Functional and Integrative Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/25/2012
Publication Date: 1/13/2013
Citation: Connor, E.E., Baldwin, R.L. 6th , Li, C., Li, R.W., Chung, H. 2013. Gene expression in bovine rumen epithelium during weaning indentifies molecular regulators of rumen development and growth. Functional and Integrative Genomics. 13:133-142.

Interpretive Summary: During weaning, the calf rumen must transition from a pre-ruminant to a true ruminant state for efficient nutrient uptake and use by the animal. During this time, the rumen increases from 30 to 70% of the capacity of the gut, significantly impacting net efficiency of feed conversion in growing cattle. To identify and characterize genes and gene networks affected by weaning in the calf rumen, global gene expression profiles were determined at different stages of development and under different dietary treatments. A total of 971 differentially genes were identified in the calf rumen that respond to weaning. These genes function primarily in free-radical scavenging and molecular transport, while the top 5 gene networks involve molecules participating in 1) fat metabolism, 2) cell morphology and cell death, 3) cellular growth and cell division, 4) molecular transport, and 5) the cell cycle. Results of these analyses provide molecular markers of rumen development, as well as identify putative gene networks regulating differentiation and growth of the rumen epithelium. This knowledge will aid in identifying targets and methods for improving and assessing rumen development and function, particularly in the growing calf.

Technical Abstract: During weaning, rumen epithelial cell function must transition from a pre-ruminant to a true ruminant state for efficient nutrient absorption and metabolism. During this time, the rumen increases from 30 to 70% of the capacity of the gut, significantly impacting net efficiency of feed conversion in growing cattle. To identify and characterize genes and gene networks affected by weaning in the calf rumen, global gene expression profiles were determined at different stages of development and under different dietary treatments. Holstein bull calves were fed commercial milk replacer only (MRO) until 42 d of age, then were provided diets of either milk + orchard grass hay (MH) or milk + grain-based commercial calf starter (MG). Calves were sacrificed at 4 time points: d 14 (n = 3) and d 42 (n = 3) of age while fed the MRO diet, and d 56 (n = 3/diet) and d 70 (n = 3/diet) while fed the MH and MG diets for RNA extraction from rumen epithelium and subsequent transcript profiling using a custom bovine whole-genome microarray. Principal components analysis indicated that gene expression patterns were separated by diet but not by developmental stage within diet. Differential expression among selected diets and time points was assessed using a robust implementation of permutation testing, a false discovery rate < 5%, and an estimated fold change = 1.5. A total of 971 differentially expressed gene transcripts was identified in response to weaning. Ingenuity Pathway Analysis Software indicated the top molecular and cellular functions of these genes are free-radical scavenging and molecular transport (P < 0.05), while the top 5 gene networks (each containing at least 27 directly interacting genes) involved molecules participating in 1) lipid metabolism, 2) cell morphology and death, 3) cellular growth and proliferation, 4) molecular transport, and 5) the cell cycle. Lastly, based on the genes impacted by weaning and their fold changes, activation of the transcription factor PPAR-alpha (P < 0.0001) was identified as an important regulator of molecular changes in the rumen epithelium during the transition from prerumination to rumination. Results of these analyses provide molecular markers of rumen development, as well as identify putative gene networks regulating differentiation and growth of the rumen epithelium. This knowledge will aid in identifying targets and methods for improving and assessing rumen development and function, particularly in the growing calf.