Explore the vast range of titles available.

Aspects of neutrophil function are diminished or dysregulated in dairy cows in the weeks just before and after calving, which appears to be an important contributor to the occurrence of retained placenta, mastitis, metritis and endometritis. The timing and mechanisms by which specific elements of neutrophil function are impaired are only partially understood. Oxidative burst capacity is the element of neutrophil function most consistently shown to be impaired in the week after calving, but that observation may partially be biased because oxidative burst has been studied more than other functions. There is sufficient evidence to conclude that the availability of calcium and glucose, and exposure to elevated concentrations of non-esterified fatty acids or β-hydroxybutyrate affect some aspects of neutrophil function. However, these factors have mostly been studied in isolation and their effects are not consistent. Social stressors such as a competitive environment for feeding or lying space should plausibly impair innate immune function, but when studied under controlled conditions such effects have generally not been produced. Similarly, treatment with recombinant bovine granulocyte colony-stimulating factor consistently produces large increases in circulating neutrophil count with modest improvements in function, but this does not consistently reduce the incidence of clinical diseases thought to be importantly attributable to impaired innate immunity. Research is now needed that considers the interactions among known and putative risk factors for impaired neutrophil function in dairy cows in the transition period.

A genome-wide association study of resistance to retained placenta (RETP) using 632,212 Holstein cows and 74,747 SNPs identified 200 additive effects with p-values < 10−8 on thirteen chromosomes but no dominance effect was statistically significant. The regions of 87.61–88.74 Mb of Chr09 about 1.13 Mb in size had the most significant effect in LOC112448080 and other highly significant effects in CCDC170 and ESR1, and in or near RMND1 and AKAP12. Four non-ESR1 genes in this region were reported to be involved in ESR1 fusions in humans. Chr23 had the largest number of significant effects that peaked in SLC17A1, which was involved in urate metabolism and transport that could contribute to kidney disease. The PKHD1 gene contained seven significant effects and was downstream of another six significant effects. The ACOT13 gene also had a highly significant effect. Both PKHD1 and ACOT13 were associated with kidney disease. Another highly significant effect was upstream of BOLA-DQA2. The KITLG gene of Chr05 that acts in utero in germ cell and neural cell development, and hematopoiesis was upstream of a highly significant effect, contained a significant effect, and was between another two significant effects. The results of this study provided a new understanding of genetic factors underlying RETP in U.S. Holstein cows.

Senescence in placental cells impacts physiological functions and contributes to pathology. Therefore, we examined biochemical markers of cellular senescence—p38, P-p38, p21, and p53—during pregnancy, at parturition, and in cases of retained fetal membranes. Placentomes were collected from pregnant cows (2nd, 4th, and 5th months of gestation) and parturient cows undergoing cesarean section, categorized as NR or RFM. Samples were separated into maternal and fetal parts and analyzed via WB and ELISA. WB confirmed protein presence, while ELISA showed a significant increase in the concentrations of both p38 and P-p38 in the fetal part in the 5th month of gestation as compared to earlier months. No significant differences were observed in the maternal part across pregnancy and parturition. These findings suggest p38 and P-p38 may be important molecules regulating the normal development of the bovine placenta during middle pregnancy. Further studies are needed to elucidate the mechanisms of their action.

Retained placenta is a common health issue, and appropriate prevention strategies are effective in postpartum health management. This study aimed to evaluate whether early intervention using GYS can prevent retained placenta and puerperal metritis, as well as enhance reproductive outcomes in cows. Each bovine in the GYS group (n = 591) received a single prophylactic dose of GYS (0.5 g/kg body weight) orally within 2 h after parturition, while those in the control group (n = 598) received no intervention. GYS treatment was associated with a decreased incidence of retained placenta (4.6% vs. 12.0%, P  < 0.01, OR = 0.335), a lower puerperal metritis risk (8.8% vs. 20.1%, P  < 0.01, OR = 0.369), and a reduced need for additional therapeutic antibiotics (11.2% vs. 26.1%, P  < 0.01, OR = 0.342). We observed increases in the first service conception rate (59.7% vs. 49.1%, P  < 0.01) and conception rate within 305 days postpartum (93.2% vs. 85.5%, P  < 0.01) in the GYS group than in the control group. A significant decrease was observed in the number of services per conception (1.8 ± 1.1 vs. 2.1 ± 1.4, P  < 0.01) and the calving-to-conception interval (83.6 ± 39.6 vs. 96.6 ± 52.5 days, P  < 0.01) between the two groups. Additionally, GYS treatment increased milk yield on days 7, 14, and 28 postpartum without affecting milk fat, milk protein, somatic cell count (SCC), or milk urea nitrogen (MUN) on days 7 and 28 postpartum. Accordingly, the GYS was effective and safe in preventing retained placenta and to improve reproductive performance in cows. Therefore, it could be a prophylactic intervention for superior postpartum fertility in cows.

Background Retained placenta (RP) is a prevalent disorder in cattle with many health-related and economic costs for the farm owners. Its etiology has not been clarified yet and there is no definite therapy for this disorder. In this study we conducted RNA-seq, hematologic and histologic experiments to survey the causes of RP development. Methods Blood samples were collected from 4 RP and 3 healthy cows during periparturtion period for hematological assessments followed by placentome sampling within 30 min after parturition. Cows were grouped as RP and control in case the placenta was retained or otherwise expelled, respectively. Total RNA was extracted from placentome samples followed by RNA-sequencing. Results We showed 240 differentially expressed genes (DEGs) between the RP and control groups. Enrichment analyzes indicated immune system and lipid metabolism as prominent over- and under-represented pathways in RP cows, respectively. Hormonal assessments showed that estradiol-17β (E2) was lower and cortisol tended to be higher in RP cows compared to controls at the day of parturition. Furthermore, histologic experiment showed that villi-crypt junctions remain tighter in RP cows compared to controls and the crypts layer seemed thicker in the placentome of RP cows. Complete blood cell (CBC) parameters were not significantly different between the two groups. Conclusion Overall, DEGs derived from expression profiling and these genes contributed to enrichment of immune and lipid metabolism pathways. We suggested that E2 could be involved in development of RP and the concentrations of P4 and CBC counts periparturition might not be a determining factor.

The objective of this study was to determine if parity affected the effect of pegbovigrastim (PEG) treatment on white blood cell (WBC) counts in grazing dairy cows. Additionally, the association of prepartum body condition score (BCS) and non-esterified fatty acid (Pre-NEFA) concentration with WBC counts was investigated. The effect of early-lactation disease was included in the statistical analysis. A randomized controlled trial on four commercial grazing dairy farms was performed. Holstein primiparous (Control = 87, PEG = 89) and multiparous (Control = 181, PEG = 184) cows were randomly assigned to one of two treatments: first PEG dose 8 ± 5 (mean ± SD) days before the expected calving date and a second dose within 24 h after calving (PEG) compared to untreated controls (Control). Treatment effects were evaluated with mixed linear regression models. Treatment with PEG increased WBC, neutrophil, lymphocyte and monocyte counts at 6 ± 1 (mean ± SD) days in milk. Parity, BCS and their interactions with treatment were not associated with WBC counts. In control cows, Pre-NEFA concentration was associated with reduced WBC, neutrophil and lymphocyte counts and tended to be associated with reduced monocyte counts. Pegbovigrastim treatment reversed the negative association of Pre-NEFA concentration with neutrophil and monocyte counts and tended to reverse the negative association of Pre-NEFA concentration with WBC counts. In the PEG treated group, cows diagnosed with retained placenta or metritis showed lower neutrophil counts when compared to PEG treated cows without these clinical diseases. These data confirm that PEG treatment increases WBC, neutrophil, lymphocyte and monocyte counts in grazing dairy cows and that this effect is independent of parity. Pegbovigrastim treatment reversed the negative association of Pre-NEFA concentration with neutrophil and monocyte counts, and tended to reverse the negative association of Pre-NEFA concentration with WBC counts.

The immune system during the periparturient period is impaired. At this time the most important factor causing immune-suppression in highly productive cows is metabolic stress resulting from hormonal and metabolic fluctuations, a negative energy balance, shortage of proteins, minerals and vitamins which are required to meet the demands of the fetus as well as the onset of lactation. This stress can activate the hypothalamic-pituitary-adrenocortical axis (HPA), which results in increase plasma corticosteroids. As a result, the cortisol concentration during the periparturient period increases by several folds particularly on the day of calving. Cortisol is a powerful immune-suppressive agent. During stress, this hormone causes depression of the leukocyte proliferation and their functions. Decreased phagocytosis of neutrophils, decreased cytotoxic ability of lymphocytes, as well as depressed activity of their cytokines, make it impossible for the normal, efficient maternal immune recognition and rejection of fetal membranes (as a foreign, allogeneic tissue expressed fetal antigens—MHC class I proteins by trophoblast cells) and finally results in their retention in cows. The metabolic periparturient stress also activates production of catecholamines, especially adrenalin. Adrenalin activates adrenoreceptors of the myometrium and then causes hypotony or atony of the uterus. Thus, cortisol and adrenalin inhibit rejection and expulsion of fetal membranes and cause their retention. These mechanisms of retained placenta (RP) often have a metabolic etiology and occur in herds, where important infectious diseases causing placentitis are absent or prevented. The aim of this article is to show the fundamental mechanisms occurring during periparturient stress and the accompanied immune-suppression in cows, as well as their consequences in relation to RP. The paper also gives examples of the symptomatic prevention of RP in cows caused by metabolic and immune suppressive factors. The prevention of RP was carried out using drugs which inhibit the activity of cortisol or adrenalin in dairy cows during calving.

Retained fetal membranes (RFM) is an important reproductive disease in dairy cows, caused by maternal and fetal placental tissue adhesion. The main collagen in maternal and fetal placenta tissues is collagen type IV (COL-IV) and its breakdown is the key to placental expulsion. Focal adhesion kinase (FAK) has been shown to regulate the hydrolysis of Col-IV by affecting the activity of MMP-2 and MMP-9 activity, but the regulation of the mechanisms involved in placenta expulsion in dairy cows after postpartum are still unclear. The aim of this study was to investigate the pathogenic mechanism of RFM by studying the relationship between the FAK signaling pathway and COL-IV regulation. Maternal placental tissues were collected from six healthy and six cows with RFM of similar age, parity, body condition and milk yield at 12 h postpartum. In vitro experiments were performed on bovine endometrial epithelial cells from three groups including a FAK inhibitor group, a FAK activator group and a control group without FAK inhibitor and activator. The abundance of molecules involved in the FAK signaling pathway and COL-IV was detected by immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The immunohistochemical results showed that the key molecules of FAK signaling pathway FAK, Src, MMP-2 and MMP-9 and Col-IV were expressed in placental tissues. The expression level of FAK, Src, MMP-2, and MMP-9 were significantly down-regulated ( P  < 0.05) and the abundances of COL-IV were significantly up-regulated ( P  < 0.05) in maternal placental tissues of RFM cows compared with healthy cows. In the FAK inhibitor treatment group, the relative expression levels of FAK and other related proteins were significantly down-regulated ( P  < 0.05) and the relative expression levels of COL-IV were significantly up-regulated ( P  < 0.05) with the results of the FAK activation group the opposite. These results indicated that FAK in maternal endometrial epithelial cells could regulate the hydrolysis process of Col-IV through the expression of key factors of signaling pathways and promote collagen hydrolysis, which in turn facilitated the process of postpartum placenta expulsion in dairy cows.

A targeted quantitative metabolomics approach was used to study temporal changes of serum metabolites in cows that normally released their fetal membranes and those that retained the placenta. We identified and measured serum concentrations of 128 metabolites including amino acids, acylcarnitines, biogenic amines, glycerophospholipids, sphingolipids and hexose at −8 and −4 weeks before parturition, during the week of retained placenta (RP) diagnosis, and at +4 and +8 weeks after parturition. In addition, we aimed at identifying metabolite signatures of pre-RP in the serum that might be used as predictive biomarkers for risk of developing RP in dairy cows. Results revealed major alterations in the metabolite fingerprints of pre-RP cows starting as early as −8 weeks before parturition and continuing as far as +8 weeks after calving. Biomarker candidates found in this study are mainly biomarkers of inflammation which might not be specific to RP. Therefore, the relevance of serum Lys, Orn, acetylornithine, lysophophatidylcholine LysoPC a C28:0, Asp, Leu and Ile as potential serum biomarkers for prediction of risk of RP in dairy cows will have to be tested in the future. In addition, lower concentrations of LysoPCs, Trp, and higher kynurenine in the serum during prepartum and the week of occurrence of RP suggest involvement of inflammation in the pathobiology of RP.

Retained placenta (RP), a quite common disorder in dairy cows, shows a high negative impact on their health status and milk production. To investigate the difference in the serum proteome between the cows with RP and the physiologic puerperium (PP). Analysis of serum samples from nine cows with RP and six with PP using high-resolution liquid chromatography-tandem mass spectrometry approach. The proteins differing in the relative abundance between the PP and RP groups were classified using the Protein Analysis Through Evolutionary Relationship tool. For the pathway enrichment analysis, the REACTOME tool, with the human genome as the background, was employed. The criterion for significance was the false discovery rate corrected P-value less than 0.05. In total 651 proteins were identified with altered relative abundance of ten proteins. Among them, seven had higher, and three showed lower relative abundance in RP than in the PP group. The differently abundant proteins participated in 15 pathways: six related to hemostasis, three involved in lipoprotein metabolism, and the remaining ones associated with for instance redox homeostasis, post-translational modification, and scavenging. Finally, the validation of the proteomic results showed that haptoglobin and lipopolysaccharide-binding protein levels reliably differentiated between the RP and PP groups. The pattern of serum proteome alterations in the cows with RP mirrored several interplaying mechanisms underlying the systematic response to the presence of RP, therefore representing a source to mine for predictive or prognostic biomarkers.