Hepatic global transcriptomic profiles of Holstein cows according to parity reveal age-related changes in early lactation

Cheng, Zhangrui; Ferris, Conrad; Crowe, Mark; Ingvartsen, Klaus; Grelet, Clément; Vanlierde, Amélie; Foldager, Leslie; Becker, Frank; Wathes, D Claire; Consortium, GplusE

Abstract

Cows can live for over 20 years, but their productive lifespan averages only around 3 years after first calving. Liver dysfunction can reduce lifespan by increasing the risk of metabolic and infec-tious disease. This study investigated the changes in hepatic global transcriptomic profiles in early lactation Holstein cows in different lactations. Cows were grouped as primiparous (lactation number 1, PP, n=41), or multiparous with lactation numbers 2-3 (MP2-3, n=87) or 4-7 (MP4-7, n=40). Liver biopsies were collected at around 14 days after calving for RNA sequencing. Blood metabolites and milk yields were measured and energy balance calculated. There were extensive differences in hepatic gene expression between MP and PP cows, with 568 differentially ex-pressed genes (DEGs) between MP2-3 and PP cows and 719 DEGs between MP4-7 and PP cows, with downregulated DEGs predominating in MP cows. The differences between the two age groups of MP cows were moderate (82 DEGs). Compared with the PP cows, MP cows had re-duced immune functions in many aspects (e.g. bacterial killing process). MP cows had increased gluconeogenesis (upregulated PC, FBP2, downregulated PDX1, C1QTNF3) but also evidence of impaired liver functionality. The MP cows had dysregulated protein synthesis (e.g. upregulated FBXW5, HSPA1A, HSPA2, HSPA6) and glycerophosholipid metabolism (e.g. GAL3ST1, GLYCTK, GPAT3, PLA2G1B) and impaired genome and RNA stability (upregulated DUSP3, downregulated IGF2BP2 and IGF2BP3) and nutrient transport (22 differentially expressed solute carrier (SLC) transporters). Genes associated with cell cycle arrest, apoptosis (CDKN2A, GRAMD4) and pro-duction of antimicrobial peptides (HAMP, LTF, LYZ, PTX3) were upregulated. More surprisingly, evidence of hepatic inflammation leading to fibrosis was present in the primiparous cows as they started their first lactation (upregulated NOD-like receptor signalling pathway and collagen synthesis). Our study suggests that the higher milk yields and lower energy balance associated with increasing lactation number came at a cost of healthy liver function and the ageing process was accelerated when cows entered their second lactation. This may increase culling due to an inability to cope adequately with metabolic and infectious diseases.

Citation

Cheng, Z., Ferris, C., Crowe, M., Ingvartsen, K., Grelet, C., Vanlierde, A., …Consortium, G. (2023). Hepatic global transcriptomic profiles of Holstein cows according to parity reveal age-related changes in early lactation. International Journal of Molecular Sciences, https://doi.org/10.3390/ijms24129906

• Journal Article Type: Article
• Acceptance Date: Jun 6, 2023
• Publication Date: Jun 8, 2023
• Deposit Date: Apr 27, 2023
• Publicly Available Date: Jun 9, 2023
• Print ISSN: 1661-6596
• Publisher: MDPI
• Peer Reviewed: Not Peer Reviewed
• DOI: https://doi.org/10.3390/ijms24129906