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

TY - JOUR

T1 - Hepatic global transcriptomic profiles of Holstein cows according to parity reveal age-related changes in early lactation

AU - Cheng, Zhangrui

AU - Ferris, Conrad

AU - Crowe, Mark A.

AU - Ingvartsen, Klaus L.

AU - Grelet, Clement

AU - Vanlierde, Amelie

AU - Foldager, Leslie

AU - Becker, Frank

AU - Wathes, D. Claire

AU - GplusE Consortium

AU - Rousing, Tine

AU - Østergaard, Søren

AU - Sørensen, Martin Tang

PY - 2023/6

Y1 - 2023/6

N2 - 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 infectious disease. This study investigated the changes in hepatic global transcriptomic profiles in early lactation Holstein cows in different lactations. Cows from five herds were grouped as primiparous (lactation number 1, PP, 534.7 ± 6.9 kg, n = 41), or multiparous with lactation numbers 2–3 (MP2–3, 634.5 ± 7.5 kg, n = 87) or 4–7 (MP4–7, 686.6 ± 11.4 kg, 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 was calculated. There were extensive differences in hepatic gene expression between MP and PP cows, with 568 differentially expressed 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). The gene expression differences suggested that MP cows had reduced immune functions compared with the PP cows. MP cows had increased gluconeogenesis but also evidence of impaired liver functionality. The MP cows had dysregulated protein synthesis and glycerophospholipid metabolism, and impaired genome and RNA stability and nutrient transport (22 differentially expressed solute carrier transporters). The genes associated with cell cycle arrest, apoptosis, and the production of antimicrobial peptides were upregulated. More surprisingly, evidence of hepatic inflammation leading to fibrosis was present in the primiparous cows as they started their first lactation. This study has therefore shown that the ageing process in the livers of dairy cows is accelerated by successive lactations and increasing milk yields. This was associated with evidence of metabolic and immune disorders together with hepatic dysfunction. These problems are likely to increase involuntary culling, thus reducing the average longevity in dairy herds.

AB - 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 infectious disease. This study investigated the changes in hepatic global transcriptomic profiles in early lactation Holstein cows in different lactations. Cows from five herds were grouped as primiparous (lactation number 1, PP, 534.7 ± 6.9 kg, n = 41), or multiparous with lactation numbers 2–3 (MP2–3, 634.5 ± 7.5 kg, n = 87) or 4–7 (MP4–7, 686.6 ± 11.4 kg, 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 was calculated. There were extensive differences in hepatic gene expression between MP and PP cows, with 568 differentially expressed 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). The gene expression differences suggested that MP cows had reduced immune functions compared with the PP cows. MP cows had increased gluconeogenesis but also evidence of impaired liver functionality. The MP cows had dysregulated protein synthesis and glycerophospholipid metabolism, and impaired genome and RNA stability and nutrient transport (22 differentially expressed solute carrier transporters). The genes associated with cell cycle arrest, apoptosis, and the production of antimicrobial peptides were upregulated. More surprisingly, evidence of hepatic inflammation leading to fibrosis was present in the primiparous cows as they started their first lactation. This study has therefore shown that the ageing process in the livers of dairy cows is accelerated by successive lactations and increasing milk yields. This was associated with evidence of metabolic and immune disorders together with hepatic dysfunction. These problems are likely to increase involuntary culling, thus reducing the average longevity in dairy herds.

KW - liver

KW - ageing

KW - cellular senescence

KW - transcriptome

KW - immunity

KW - metabolism

KW - lactation

KW - age

KW - cows

KW - Transcriptome

KW - Lactation/genetics

KW - Pregnancy

KW - Milk/metabolism

KW - Animals

KW - Cattle

KW - Liver/metabolism

KW - Female

KW - Parity

UR - http://www.scopus.com/inward/record.url?scp=85163980274&partnerID=8YFLogxK

U2 - 10.3390/ijms24129906

DO - 10.3390/ijms24129906

M3 - Journal article

C2 - 37373054

SN - 1661-6596

VL - 24

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 12

M1 - 9906

ER -