Abstract
The complex etiology and pathogenesis of retained placenta (RP) bring huge challenges for researchers and clinical veterinarians in investigating the pathogenesis and treatment schedule. This study aims to investigate the pathogenesis of RP in dairy cows by plasma metabolomics. As subjects, 10 dairy cows with RP and 10 healthy dairy cows were enrolled according to strict enrollment criteria. Imbalanced antioxidant capacity, reduced Th1/Th2 cytokine ratio, and deregulation of total bilirubin (T-bil), alkaline phosphatase (ALP), and reproductive hormones were shown in dairy cows with RP by detecting biochemical indicators, oxidation and antioxidant markers, and cytokines in serum. Plasma metabolites were detected and analyzed by a liquid chromatography–mass spectrometry (LC–MS) system coupled with multivariate statistical analysis software. A total of 23 potential biomarkers were uncovered in the plasma of dairy cows with RP. The metabolic pathways involved in these potential biomarkers are interconnected, and the conversion, utilization, and excretion of nitrogen were disturbed in dairy cows with RP. Moreover, these potential biomarkers are involved in the regulation of antioxidant capacity, inflammation, and autocrine or paracrine hormone. All of these findings suggest that an imbalance of these potential biomarkers might be responsible for the imbalanced antioxidant capacity, reduced Th1/Th2 cytokine ratio, and deregulation of reproductive hormones in dairy cows with RP. The regulation of metabolic pathways involved in these potential biomarkers represents a promising therapeutic strategy for RP.
Highlights
The retained placenta (RP), a common multifactorial postpartum reproductive disease manifesting as failure to expel fetal membranes within 24 h of calving, increases the risk of developing metritis and infertility and reduces milk production and quality, causing great financial losses in the dairy industry [1,2,3,4]
The metabolic profiles of plasma samples from healthy and diseased groups were clearly separated in the negative and positive modes. These findings suggest that the plasma metabolic profile of dairy cows with RP was significantly different from that of healthy dairy cows (Figures 1A,B)
In the partial least squares discriminant analysis (PLS-DA) model, the samples of the disease and healthy groups were clearly separated (Figures 1C,D), and the Q2 regression lines based on a permutation test with a negative intercept suggested that the model was not overfitting (Figures 1E,F)
Summary
The retained placenta (RP), a common multifactorial postpartum reproductive disease manifesting as failure to expel fetal membranes within 24 h of calving, increases the risk of developing metritis and infertility and reduces milk production and quality, causing great financial losses in the dairy industry [1,2,3,4]. The etiology, pathogenesis, and therapy of RP have been extensively explored by many researchers [4,5,6,7]. The complex etiology and pathogenesis bring huge challenges. Potential Biomarkers of Retained Placenta for researchers and clinical veterinarians in probing the pathogenesis and treatment schedule of RP [9,10,11,12]. Many studies have confirmed that changes in blood metabolites, cytokines, inflammatory factors, immune factors, and hormones are associated with the pathogenesis of RP [3, 13, 16, 17]. It is difficult to clarify the complex pathogenesis of RP involving the nutritional metabolic, immune, nervous, and reproductive systems through blood indicators
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