At dry off, the mammary gland of the early dry cow undergoes a multitude of morphologic, immunologic, metabolic, and biochemical alterations known as mammary gland involution. During involution, the mammary gland is vulnerable to bacterial infection, particularly if milk leakage occurs. Increased risk of milk leakage and infection are associated with high milk production at dry off. Therefore, as advances in dairy cow management and fertility continue to increase milk production- more cows will be at risk for infection during early mammary involution. However, much remains unknown about optimizing mammary involution.
Biomarkers are biological observations that are indicative of specific physiologic processes and can be used to characterize, predict, or monitor physiological outcomes. Biomarkers for mammary gland involution, such as lactoferrin, are commonly used by researchers to quantify to onset and degree of mammary involution. The association between these commonly used biomarkers with mammary gland health and milk production is currently unknown. To address this, my dissertation was centered around the association of certain biomarkers (fat soluble vitamins and lipid mediators) with mammary gland involution, oxidative stress, and diseases in dairy cows.
In our first experiment we analyzed the association of serum retinol, β-carotene, 25-hydroxyvitamin D, and α-tocopherol concentrations from dry off through 7 days in lactation with transition cow diseases, milk production, and oxidative stress. Overall, we found that decreased serum retinol was associated with increased incidence of hyperketonuria, uterine disease, and with having any disease during the transition period. Increased serum 25-hydroxyvitamin D was associated with antioxidant potential during the transition period. There results demonstrated that serum vitamin concentrations could be utilized as biomarkers for health and oxidative stress.
In our second experiment we analyzed lipid mediators, such as polyunsaturated fatty acids, oxylipids, and isoprostanes in plasma and milk during mammary gland involution. These lipid mediators are essential factors affecting the magnitude and duration of the inflammatory response generated during early mammary gland involution. In blood, concentrations of these lipid mediators tended to fluctuate only on the first 1 to 2 days post dry off and had much larger fluctuations post calving. Lipid mediators in milk, however, increased to their greatest concentration 7 days post dry off compared to any other time point around dry off or after calving. This may indicate that the inflammatory processes occurring during early mammary gland involution are different in timing and magnitude in the mammary gland compared to the rest of the body. This could decrease the reliability of certain blood biomarkers used to evaluate mammary gland involution.
Retinoic acid, the active form of vitamin A, has a multitude of biological functions that could affect different aspects of mammary gland involution. We analyzed plasma concentrations of 3 retinoic acid isomers (all-trans retinoic acid, 9-cis retinoic acid, and 13-cis retinoic acid) during the transition from lactation to mammary gland involution using liquid chromatography tandem mass spectometry. Additionally, I created polynomial regression models to investigate the association of retinoic acid with biomarkers associated with mammary gland involution, inflammation, and oxidative stress. All 3 retinoic acid isomers decreased in plasma after dry off. All-trans retinoic acid was associated with total daily milk yield the day before dry off, serum reactive oxygen species, serum haptoglobin, and milk citrate during the transition from lactation to mammary gland involution. These results suggested that all-trans retinoic acid may have effects on inflammation and oxidative stress. All together these data suggest that serum vitamins and lipid mediators could be inciteful biomarkers for mammary gland involution. However, factors such as sample type (blood or milk) and individual cow factors (milk production) are important considerations when evaluating mammary gland involution with biomarkers.
Jaimie Strickland, DVM, MS, PhD is a dairy veterinarian from Lansing, Michigan. She recently received her PhD from the Comparative Medicine and Integrated Biology department in the College of Veterinary Medicine at Michigan State University under the mentorship of Drs. Lorraine Sordillo and Pamela Ruegg. Her interests include immunology, data analysis, and science communication.
Text and picture: Jaimie Strickland