Understanding the regulatory mechanisms of milk production using integrative transcriptomic and proteomic analyses: improving inefficient utilization of crop by-products as forage in dairy industry.

Bovine milk is an important nutrient source for humans. Forage plays a vital role in dairy husbandry via affecting milk quality and quantity. However, the differences in mammary metabolism of dairy cows fed different forages remain elucidated. In this study, we utilized transcriptomic RNA-seq and iTRAQ proteomic techniques to investigate and integrate the differences of molecular pathways and biological processes in the mammary tissues collected from 12 lactating cows fed corn stover (CS, low-quality, n = 6) and alfalfa hay (AH, high-quality, n = 6). A total of 1631 differentially expressed genes (DEGs; 1046 up-regulated and 585 down-regulated) and 346 differentially expressed proteins (DEPs; 138 increased and 208 decreased) were detected in the mammary glands between the CS- and AH-fed animals. Expression patterns of 33 DEPs (18 increased and 15 decreased) were consistent with the expression of their mRNAs. Compared with the mammary gland of AH-fed cows, the marked expression changes found in the mammary gland of CS group were for genes involved in reduced mammary growth/development (COL4A2, MAPK3, IKBKB, LGALS3), less oxidative phosphorylation (ATPsynGL, ATP6VOA1, ATP5H, ATP6VOD1, NDUFC1), enhanced lipid uptake/metabolism (SLC27A6, FABP4, SOD2, ACADM, ACAT1, IDH1, SCP2, ECHDC1), more active fatty acid beta-oxidation (HMGCS1), less amino acid/protein transport (SLC38A2, SLC7A8, RAB5a, VPS18), reduced protein translation (RPS6, RPS12, RPS16, RPS19, RPS20, RPS27), more proteasome- (PSMC2, PSMC6, PSMD14, PSMA2, PSMA3) and ubiquitin-mediated protein degradation (UBE2B, UBE2H, KLHL9, HSPH1, DNAJA1 and CACYBP), and more protein disassembly-related enzymes (SEC63, DNAJC3, DNAJB1, DNAJB11 and DNAJC12). Our results indicate that the lower milk production in the CS-fed dairy cows compared with the AH-fed cows was associated with a network of mammary gene expression changes, importantly, the prime factors include decreased energy metabolism, attenuated protein synthesis, enhanced protein degradation, and the lower mammary cell growth. The present study provides insights into the effects of the varying quality of forages on mammary metabolisms, which can help the improvement of strategies in feeding dairy cows with CS-based diet.