Cheng, ZhangruiMcLaughlin, Danielle L.Little, Mark W.Ferris, ConradSalavati, MazdakIngvartsen, Klaus L.,Crowe, Mark A.Wathes, D. Clairethe GplusE Consortium2023-02-072023-02-072022-12-20Cheng, Z., McLaughlin, D.L., Little, M.W., Ferris, C., Salavati, M., Ingvartsen, K.L., Crowe, M.A. and Wathes, D.C. (2022) ‘Proportion of Concentrate in the Diet of Early Lactation Dairy Cows Has Contrasting Effects on Circulating Leukocyte Global Transcriptomic Profiles, Health and Fertility According to Parity’, International Journal of Molecular Sciences. MDPI AG. Available at: https://doi.org/10.3390/ijms24010039.1422-00671661-6596https://doi.org/10.3390/ijms24010039Publication history: Accepted - 16 December 2022; Published online - 20 December 2022The functionality of circulating leukocytes in dairy cows is suppressed after calving, with negative energy balance as a risk factor. Leukocyte transcriptomic profiles were compared separately in 44 multiparous (MP) and 18 primiparous (PP) Holstein–Friesian cows receiving diets differing in concentrate proportion to test whether immune dysfunction could be mitigated by appropriate nutrition. After calving, cows were offered either (1) low concentrate (LC); (2) medium concentrate (MC) or (3) high concentrate (HC) diets with proportions of concentrate to grass silage of 30%:70%, 50%:50% and 70%:30%, respectively. Cow phenotype data collected included circulating metabolites, milk yield and health and fertility records. RNA sequencing of circulating leukocytes at 14 days in milk was performed. The HC diet improved energy balance in both age groups. There were more differentially expressed genes in PP than MP cows (460 vs. 173, HC vs. LC comparison) with few overlaps. The MP cows on the LC diet showed upregulation of the complement and coagulation cascade and innate immune defence mechanisms against pathogens and had a trend of more cases of mastitis and poorer fertility. In contrast, the PP cows on the HC diet showed greater immune responses based on both gene expression and phenotypic data and longer interval of calving to conception. The leukocytes of MP and PP cows therefore responded differentially to the diets between age, nutrient supply and immunity affecting their health and subsequent fertility.en© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).postpartum immunosuppressioninnate immunitymetabolismleukocyteslactation dietstranscriptomereproductioncowsArticle