Efforts to optimize the longevity of dairy cows are hindered by the increased risk of adverse health events, culling or dying on farm with increased parity. Lipidomics provides a platform to help identify important biomarkers and biological pathways associated with increased parity and associated aging. A large, multi-site (15 pasture-based, 15 TMR farms) cross-sectional study collected plasma samples from nonlactating, late pregnant, 'dry' cow (696 cows, ~27 d prepartum) and peak-milk cows (796 cows, ~58 DIM) in a disproportionate stratified (parity: 0, 1, 2, > 2 for dry cows; 1, 2, 3, > 3 for peak-milk cows) random sampling frame. A total of 185 lipid species, comprising the lipids classes of phospholipids, sphingomyelins (SM) and triacylglycerols, were quantified in a targeted, liquid chromatography-mass spectrometry (LC-MS) approach. Dry and peak-milk cohorts were analyzed separately throughout. Variation in lipid profiles was mostly attributed to farm of origin (36-41% of variation), with feeding system explaining 13-21% and parity 6-9%, according to ANOVA simultaneous component analysis (ASCA) modeling. Multiple linear regression (MLR) and orthogonal-partial least squares (O-PLS) investigated the association of the lipid profile with age (d), while discriminate analysis compared 1st parity with > 3 parity cows in O-PLS discriminate analysis (O-PLS-DA), random forest (RF) and support vector machine (SVM) models. Rankings of the most important lipid species for each model type were compared. Phospholipids with 40 carbon atoms and 6 double bond equivalents (40:6) were consistently decreased with increasing parity and age across both dry and peak-milk cohorts. These lipids most likely contained stearate (18:0) and docosahexaenoic acid (DHA, C22:6;n-3), an omega-3 fatty acid. Additionally, phospholipids with 40:5, 38:6, lysophosphatidylcholine (17:0), SM(35:1), and SM(35:2) were commonly identified lipids that decreased in concentration with parity and age. Docosahexaenoic acid has been associated with improved cattle health, reproduction, and milk production and quality. This study raises the hypothesis that reduced DHA levels in older cows may be a significant factor increasing susceptibility to adverse health events, reduced reproductive performance, and herd removal. Studies that supplement DHA or its precursors can test this hypothesis and may be important in optimizing longevity of cows.
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