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Associations between Circulating IGF-1 Concentrations and Disease Status with the Leukocyte Transcriptome in Early Lactation Dairy Cows

Wathes, D Claire; Becker, Frank; Buggiotti, Laura; Crowe, Mark A; Ferris, Conrad; Foldager, Leslie; Grelet, Clément; Hostens, Miel; Ingvartsen, Klaus L; Marchitelli, Cinzia; Salavati, Mazdak; Signorelli, Federica; Takeda, Haruko; Tang, Lijing; Cheng, Zhangrui; GplusE consortium


D Claire Wathes

Frank Becker

Laura Buggiotti

Mark A Crowe

Conrad Ferris

Leslie Foldager

Clément Grelet

Miel Hostens

Klaus L Ingvartsen

Cinzia Marchitelli

Mazdak Salavati

Federica Signorelli

Haruko Takeda

Lijing Tang

Zhangrui Cheng

GplusE consortium


Peripartum dairy cows commonly experience negative energy balance (EB) and immunosuppression together with high incidences of infectious and metabolic disease. This study investigated mechanisms linking EB status with immune defence in early lactation. Data were collected from multiparous Holstein cows from six herds and leukocyte transcriptomes were analysed using RNA sequencing. Global gene expression was related to circulating IGF-1 (as a biomarker for EB) by subdividing animals into three groups, defined as IGF-1 LOW (100 ng/ml, n=43) at 14 ± 4 days in milk (DIM). Differentially expressed genes between groups were identified using CLC Genomics Workbench V21, followed by cluster and KEGG pathway analysis, focussing on the comparison between LOW and HIGH IGF-1 cows. LOW cows were older and had significantly lower dry matter intakes and EB values, whereas HIGH cows produced more milk. During the first 35 DIM, 71% of LOW cows had more than one health problem v 26% HIGH cows, including more with clinical mastitis and uterine infections. Gene expression analysis indicated that leukocytes in LOW cows switched energy metabolism from oxidative phosphorylation to aerobic glycolysis (PGM, LDH, PDK4). Many antimicrobial peptides were up-regulated in LOW cows (e.g. PTX3, DMBT1, S100A8, S100A9) together with genes associated with inflammation, platelet activation and the complement cascade. HIGH cows had greater expression of genes regulating T and B cell function and the cytoskeleton. Overall results suggested an ongoing cycle of poor EB and higher infection rates in LOW IGF-1 cows which was reflected in altered leukocyte functionality and reduced milk production.


Wathes, D. C., Becker, F., Buggiotti, L., Crowe, M. A., Ferris, C., Foldager, L., …GplusE consortium. (2021). Associations between Circulating IGF-1 Concentrations and Disease Status with the Leukocyte Transcriptome in Early Lactation Dairy Cows. Animals,

Journal Article Type Article
Acceptance Date Nov 10, 2021
Online Publication Date Nov 25, 2021
Publication Date Nov 25, 2021
Deposit Date Oct 12, 2021
Publicly Available Date Nov 25, 2021
Journal Ruminants
Publisher MDPI
Peer Reviewed Peer Reviewed
Public URL