Title: Transcriptional regulators transforming growth factor-beta 1 and estrogen-related receptor-alpha identified as putative mediators of calf rumen epithelial tissue development and function during weaning Authors
|Ellis, Steven -|
|Chung, Hoyoung -|
Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 10, 2014
Publication Date: April 25, 2014
Citation: Connor, E.E., Baldwin, R.L., Walker, M.P., Ellis, S., Li, C., Kahl, S., Chung, H., Li, R.W. 2014. Transcriptional regulators transforming growth factor-beta 1 and estrogen-related receptor-alpha identified as putative mediators of calf rumen epithelial tissue development and function during weaning. Journal of Dairy Science. 97:4193-4207. Interpretive Summary: The rumen is the first compartment of the digestive system of cattle. In newborn calves, the rumen is not fully functional and must undergo significant developmental changes in order to effectively process high-fiber diets of the mature animal. Rapid and complete development of the rumen is essential to successful calf rearing in animal and dairy production. It is known that the type of diet consumed by the calf, whether it be primarily in the form of hay or grain, has a significant effect on how quickly and to what extent these developmental changes occur. We examined genes and gene pathways controlling development of the rumen of newborn calves in response to hay-based diets versus grain-based diets at weaning to gain a better understanding of the regulation of this critical developmental process. The information gathered from this work will assist animal scientists and dairy producers in diet formulations to enhance and support optimal development of the rumen in the newborn animal.
Technical Abstract: Molecular mechanisms controlling rumen epithelial development at weaning remain largely unknown. To identify gene networks and regulatory factors responsive to concentrate versus forage feeding at weaning, Holstein bull calves (n = 18) were fed commercial milk replacer only (MRO) until 42 d of age. Three calves each were sacrificed at 14 and 42 d of age for tissue collection, and weaning was initiated in remaining calves by providing diets of either milk + orchard grass hay (MH; n = 6) or milk + grain-based commercial calf starter (MG; n = 6). At 56 and 70 d of age, 3 calves from the MH and MG groups were sacrificed for collection of rumen epithelium from the ventral sac. Total RNA and protein were extracted for microarray analysis and ELISA, respectively. As expected, calves fed MRO had little to no rumen papillary development and length and development of rumen papillae were greater in MG versus MH calves. Differentially expressed genes between the MRO diet at d 42 (pre-weaning) versus the MG or MH diets at d 56 (post-weaning) were identified using Permutation Analysis of Differential Expression. Expression of 345 and 519 transcripts was uniquely responsive to grain and hay feeding during weaning, respectively. Ingenuity Pathway Analysis of differentially expressed genes indicated that the top-ranked biological function impacted by grain feeding was the cell cycle, and transforming growth factor-ß1 and transcription factor forkhead box protein O1 were identified as key transcriptional regulators of genes responsive to grain feeding. The top-ranking biological function impacted by transition to a hay-based diet at weaning was energy production. Receptors for IGF-1 and insulin, and estrogen-related receptor a were identified as important transcriptional regulators of genes in rumen responsive to hay feeding. Further analysis of transforming growth factor-ß1 and estrogen-related receptor a mRNA expression in rumen epithelium obtained from Holstein calves (n = 26) from birth to 42 d of age in an independent study showed significant increases in transcript expression with advancing age, supporting their roles in mediating rumen epithelial development during weaning. Results of these analyses provide insight into molecular pathways uniquely responsive to grain or hay feeding in calf rumen epithelium during weaning, and provide targets for modulation of rumen development and function in the growing calf.