Research articleThe association of plasma glucose, BHBA, and NEFA with postpartum uterine diseases, fertility, and milk production of Holstein dairy cows
Introduction
Postpartum uterine diseases such as metritis, endometritis, purulent vaginal discharge and retained placenta (RP) are associated with substantially infertility, reduced milk yield, and increased culling rates [1]. These diseases have complex multifactorial causes which include exposure to bacterial pathogens [2], mineral and vitamin deficiencies [3], negative energy balance [4], and immunosuppression [5], [6], [7]. Previous studies have extensively demonstrated associations between negative energy balance markers, particularly nonesterified fatty acids (NEFA) and β-hydroxybutyric acid (BHBA) in plasma, and the incidence of postpartum diseases such as clinical ketosis and displaced abomasum [8], [9]. Excessive fat mobilization in dairy cows has also been associated with clinical endometritis and linked to immunosuppression [10], [11], [12]. The inflammation of the endometrium has been showed to have a detrimental effect on reproductive performance, reducing both the first-service conception rate and the overall pregnancy risk mainly due to dysregulated ovarian function and oocyte development [13], [14], [15], [16].
The liver is responsible for metabolizing circulating NEFA, which can be completely oxidized for energy production, exported from the liver as lipoproteins, or partially oxidized into BHBA and other ketone bodies [17], [18]. When the liver is overloaded with NEFA, hepatocytes increase the level of partial oxidation of NEFA, which leads to the accumulation of BHBA and other ketone bodies, eventually causing subclinical and clinical ketosis [19]. Therefore, hyperketonemia is a marker of liver health and has been associated with infectious diseases (e.g., mastitis, metritis) [3], [20].
In addition to fat mobilization in early postpartum cows, liver gluconeogenesis increases to provide glucose for synthesis of milk lactose [21]. The large demand for glucose may lower the amount of glucose available to other tissues in the body, including those that are involved in postpartum immune defense. During the period of negative energy balance, dairy cows experience a reduction in blood glucose levels and neutrophil function. Low glucose levels observed during the transition to lactation may be associated with immunosuppression. Granulocytes depend on uptake of exogenous glucose and intracellular glycogen stores for the energy required for chemotaxis, phagocytosis, and microbial killing [22], [23]. Conversely, many studies have demonstrated impaired adherence and neutrophil dysfunction associated with high glucose levels [24], [25], [26].
A strong association between decreased immune response and a greater degree of negative energy has been reported in cows that developed uterine disease compared with healthy cows [10], [12], [27], [28]. For instance, cows that developed uterine disease experienced a greater degree of negative energy balance, increased serum levels of inflammatory markers, greater blood glucose concentration at calving, and had lower intracellular neutrophil glycogen levels [20], [28]. Moreover, cows with metritis and cows with cystic ovaries had increased levels of ketone bodies than unaffected cows [29].
Besides, relationships between blood metabolites and the reproductive performance of dairy cows have been reported earlier [30], [31]. For instance, in a multivariate description of factors that influence fertility in dairy cows, Westwood et al. (2002) showed that increased concentrations of plasma glucose were associated with greater probability of estrous expression at first ovulation, whereas higher serum concentrations of NEFA lowered the probability of conception by 150 days [31], supporting previous observations where more mobilization of body tissue delayed the resumption of ovarian activity [32], However, in another study, days-to-conception was not associated with glucose levels but was inversely related to milk production [33].
Thus far, most current research has focused on the evaluation of the markers of negative energy balance, NEFA and BHBA as predictors of inflammation and postpartum diseases [8], [34], [35], whereas few studies have evaluated the importance of glucose as a potentially significant risk factor for the development of uterine diseases. Therefore, the objective of this study was to investigate associations between the metabolic indicators NEFA, BHBA, and glucose during the transition period and the occurrence of uterine diseases and the subsequent effect on fertility. Because uterine diseases have negative effect on milk production, and milk production is accompanied by changes in glucose and energy metabolism, milk yield was also evaluated.
Section snippets
Farm, management, and sample collection
This study was conducted from October 2012 until January 2013 on a dairy farm located near Ithaca, New York. In total, 181 Holstein dairy cows (108 dry cows and 73 pregnant heifers) were enrolled in the study. The farm milked 3300 Holstein cows 3 times daily in a double 52-stall parallel milking parlor. The cows were housed in freestall barns, with concrete stalls covered with mattresses and bedded with composted manure solids. All cows were offered a total mixed ration consisting of
Descriptive analysis
In total, 181 cows were studied, of which 73 were primiparous (40.3%) and 108 (59.6%) were of second parity and greater (multiparous). The overall incidences of clinical ketosis, RP, metritis, and clinical endometritis in the study population were 7.1%, 9.4%, 15%, and 22.3%, respectively. The percentage of pregnant cows within 150 days was 51.1% (n = 92).
At enrollment, the average days of gestation was 229.7 days (SE ±2.19). The median BCS at enrollment for both primiparous and multiparous cows
Discussion
The results of our study demonstrate that plasma glucose concentration is a significant risk factor for metritis and clinical endometritis. Cows that were diagnosed with metritis and subsequently with clinical endometritis had higher plasma glucose levels after parturition compared with healthy counterparts. Glucose plasma concentrations after parturition were also found to be higher in cows that had RP than in cows without RP. For predicting RP, the ROC curve with a higher AUC and LRs was for
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