Postpartum uterine diseases in dairy cows : a review with emphasis on subclinical endometritis

In this review, updated and precise definitions of the most common postpartum uterine diseases in dairy cows are provided. An aberrant uterine environment at inappropriate stages of the reproductive cycle inflicts damage to gametes and zygotes, impairing the reproductive performance of dairy cows. This involves major economic losses for the milk production unit. Consequently, an accurate diagnosis of postpartum uterine diseases is indispensable for practitioners to set up a prompt and efficient treatment. This review furthermore emphasizes on the new perspectives regarding diagnosis and treatment of subclinical endometritis, a highly prevalent uterine disease that is often overlooked by practitioners while causing major reproductive problems. Based on a more profound clinical understanding of the postpartum uterine disease complex, practitioners will be able to better use the available diagnostic tools and therefore apply a more efficient therapeutic approach

The effect of pegbovigrastim on circulating neutrophil count in dairy cattle : a randomized controlled trial

Previous research in various species has shown that granulocyte-colony stimulating factor stimulates the production and release of neutrophils from bone marrow. The objective of this study was to characterize the effects of polyethylene glycol-bound bovine granulocyte colony-stimulating factor (pegbovigrastim; Imrestor, Elanco) on circulating leukocyte counts. Thirty-four Holstein cows were randomly assigned to receive 2 injections of either physiologic saline (n = 16) or pegbovigrastim (n = 18), 7 days before expected calving (d - 7) and within 24 hours after calving (d 0). Cows were sampled at d - 7, d - 6, d 0, d + 1, d + 7, and d +/- 21, relative to calving. Only cows for which the interval from the first injection to calving was >= 4 d and <= 10 d were included, such that the interval (mean +/- SD) from first treatment to calving was 6.7 +/- 1.9 d. Treatment effects were assessed with mixed linear regression models. After the first injection, neutrophil counts (x10(9)/L) in pegbovigrastim-treated cows increased from 4.3 (95% CI 3.8 to 4.8) at d - 7 to 18.2 (CI 16.3 to 20.3) at d - 6 (P < 0.0001). Their counts then decreased from d - 6 to d 0, when the second injection was administered, at a rate of - 0.31 x 10(9) neutrophils/L/day (P < 0.0001). After the second injection, neutrophil counts increased from 16.4 (CI 13.7 to 19.6) at d 0 to 32.8 (CI 25.2 to 42.7) at d + 1 (P < 0.0001), after which counts decreased at a rate of -3.73 x 10(9) neutrophils/L/day until d + 7 (P < 0.0001). Counts continued to decrease from d + 7 to d + 21 at a slower rate of -0.43 x 10(9) neutrophils/L/day (P < 0.0001), until baseline levels were reached. Conversely, in control cows, neutrophil counts were unchanged from d - 7 to d - 6 (P = 0.86) after the first injection and then decreased from 6.1 (CI 5.0-7.3) at d 0, to 3.2 (CI 2.4-4.2) at d + 1 (P < 0.0001) after the second injection. Neutrophil count was greater (P < 0.001) in pegbovigrastim-treated than in control cows at days -6, 0, +1 and +7. Area under the curve (cells x 10(9)/L per 28 d) for neutrophil counts in the pegbovigrastim group was 429, versus 99 in the control group (P < 0.0001). The response to each injection of pegbovigrastim was additive and consisted of 95% segmented neutrophils, suggesting that the effect of the treatment was to release mature neutrophils from a substantial pool available in the bone marrow. The sustained increase in circulating neutrophil count around the time of calving may contribute to improved health during the peripartum transition period

Creating chimeras: Embryonic stem cells incorporated

Gene modification within the murine genome has become a powerful and invaluable tool to investigate development. One example of the utility of such technology is providing a method by which researchers can follow cells throughout development via the introduced genetic modifications.Fil: Pascottini, Osvaldo Bogado. University of Chicago; Estados UnidosFil: Goszczynski, Daniel Estanislao. University of Chicago; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Nguyen, Alexandra L.. University of Chicago; Estados Unido

Primary replication and invasion of the bovine gammaherpesvirus BoHV-4 in the genital mucosae

Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus that is widespread in cattle. Ex vivo models with bovine genital tract mucosa explants were set up to study molecular/cellular BoHV-4-host interactions. Bovine posterior vagina, cervix and uterus body were collected from cows at two stages of the reproductive cycle for making mucosa explants. The BoHV-4 replication kinetics and characteristics within the three different mucosae of animals in the follicular and luteal phase were assessed by virus titration. The number of plaques, plaque latitude and number of infected cells were determined by immunofluorescence. BoHV-4 replicated in a productive way in all genital mucosal tissues. It infected single individual cells in both epithelium and lamina propria of the genital mucosae at 24 hours post-inoculation (hpi). Later, small BoHV-4 epithelial plaques were formed that did not spread through the basement membrane. 50% of the number of BoHV-4 infected cells were identified as cytokeratin(+) and CD172a(+) cells in the three parts of the genital tract at 24 hpi. Upon a direct injection of genital explants with BoHV-4, fibrocytes became infected, indicating that the unidentified 50% of the infected cells are most probably fibrocytes. In this study, in vivo-related in vitro genital tract models were successfully established and the early stage of the pathogenesis of a genital infection was clarified: BoHV-4 starts with a productive infection of epithelial cells in the reproductive tract, forming small foci followed by a non-productive infection of surveilling monocytic cells which help BoHV-4 to invade into deeper tissues

Metabolic stress in the transition period of dairy cows : focusing on the prepartum period

Simple Summary Complex pathways of metabolic adaptation occur in high-yielding dairy cows around calving. These adaptations require the redirection of nutrients to support the last stages of fetal growth and the commencement of lactation. Failure to adapt to these changes may result in the development of clinical disease in the postpartum period. Therefore, most existing literature is focused on studying the metabolic changes in the postpartum period. However, some of the risk factors associated with postpartum clinical disease can already be found in the prepartum period. This review describes adaptive changes occurring in prepartum high-yielding dairy cows, from drying off (40 to 60 days before parturition) until calving. All modern, high-yielding dairy cows experience a certain degree of reduced insulin sensitivity, negative energy balance, and systemic inflammation during the transition period. Maladaptation to these changes may result in excessive fat mobilization, dysregulation of inflammation, immunosuppression, and, ultimately, metabolic or infectious disease in the postpartum period. Up to half of the clinical diseases in the lifespan of high-yielding dairy cows occur within 3 weeks of calving. Thus, the vast majority of prospective studies on transition dairy cows are focused on the postpartum period. However, predisposition to clinical disease and key (patho)physiological events such as a spontaneous reduction in feed intake, insulin resistance, fat mobilization, and systemic inflammation already occur in the prepartum period. This review focuses on metabolic, adaptive events occurring from drying off until calving in high-yielding cows and discusses determinants that may trigger (mal)adaptation to these events in the late prepartum period

Letter Ruling 12-4: Massachusetts Sales/Use Tax on"Call Tracking Service"

Previous research in various species has shown that granulocyte-colony stimulating factor stimulates the production and release of neutrophils from bone marrow. The objective of this study was to characterize the effects of polyethylene glycol-bound bovine granulocyte colony-stimulating factor (pegbovigrastim; Imrestor, Elanco) on circulating leukocyte counts. Thirty-four Holstein cows were randomly assigned to receive 2 injections of either physiologic saline (n = 16) or pegbovigrastim (n = 18), 7 days before expected calving (d -7) and within 24 hours after calving (d 0). Cows were sampled at d -7, d -6, d 0, d +1, d +7, and d +21, relative to calving. Only cows for which the interval from the first injection to calving was ≥ 4 d and ≤ 10 d were included, such that the interval (mean ± SD) from first treatment to calving was 6.7 ± 1.9 d. Treatment effects were assessed with mixed linear regression models. After the first injection, neutrophil counts (×109/ L) in pegbovigrastim-treated cows increased from 4.3 (95% CI 3.8 to 4.8) at d -7 to 18.2 (CI 16.3 to 20.3) at d -6 (P < 0.0001). Their counts then decreased from d -6 to d 0, when the second injection was administered, at a rate of -0.31 ×109 neutrophils/L/day (P < 0.0001). After the second injection, neutrophil counts increased from 16.4 (CI 13.7 to 19.6) at d 0 to 32.8 (CI 25.2 to 42.7) at d +1 (P < 0.0001), after which counts decreased at a rate of -3.73 ×109 neutrophils/L/day until d +7 (P < 0.0001). Counts continued to decrease from d +7 to d +21 at a slower rate of -0.43 ×109 neutrophils/L/day (P < 0.0001), until baseline levels were reached. Conversely, in control cows, neutrophil counts were unchanged from d -7 to d -6 (P = 0.86) after the first injection and then decreased from 6.1 (CI 5.0-7.3) at d 0, to 3.2 (CI 2.4-4.2) at d +1 (P < 0.0001) after the second injection. Neutrophil count was greater (P < 0.001) in pegbovigrastim-treated than in control cows at days -6, 0, +1 and +7. Area under the curve (cells ×109/ L per 28 d) for neutrophil counts in the pegbovigrastim group was 429, versus 99 in the control group (P < 0.0001). The response to each injection of pegbovigrastim was additive and consisted of 95% segmented neutrophils, suggesting that the effect of the treatment was to release mature neutrophils from a substantial pool available in the bone marrow. The sustained increase in circulating neutrophil count around the time of calving may contribute to improved health during the peripartum transition period

Flow cytometric assessment of the viability and functionality of uterine polymorphonuclear leukocytes in postpartum dairy cows

Postpartum dairy cows experience impaired peripheral polymorphonuclear leukocyte (PMN) functionality, which has been associated with reproductive tract inflammatory diseases. However, it has not been elucidated yet whether endometrial PMN functionality is (equally) impaired. We developed a method for endometrial PMN isolation and flow cytometric assessment of their viability and functionality. We also evaluated PMN immunolabeling, using a specific bovine granulocyte marker, CH138A. Blood and endometrial cytobrush samples were collected in duplicate from seventeen clinically healthy Holstein-Friesian cows between 9 and 37 days in milk. The proportion of viable, apoptotic, and necrotic PMN in endometrial samples roughly ranged from 10 to 80%, indicating highly dynamic endometrial PMN populations in the postpartum uteri. Endometrial PMN functionality testing revealed that PMN immunolabeling increased the accuracy, although this protocol might influence the median fluorescence intensity of the sample. Phagocytosis seemed the most stable and reliable endometrial PMN function and could be assessed satisfactorily without prior CH138A immunolabeling. However, the interpretation of oxidative burst and intracellular proteolysis tests remains challenging. The correlation between peripheral and endometrial PMN functionality was poor. Further research is warranted to unravel the role of uterine PMN viability and functionality in bovine uterine health

Lessons learned from bovine subclinical endometritis:A systematic review exploring its potential relevance to chronic endometritis in women

Chronic endometritis (CE) in humans is asymptomatic inflammation of the endometrium, associated with poor reproductive outcomes. Similarly, asymptomatic endometrial inflammation in cows, termed subclinical endometritis (SCE), is associated with adverse reproductive outcomes. While the pathophysiology and treatment options for CE in humans remain poorly defined, the well-known financial implications of SCE in dairy cows have attracted intensive research. We performed a systematic review to determine potential areas of interest in human CE research, by analysing emergent themes that arose in studies of SCE in cows. A literature search for studies of subclinical endometritis in cows published between 1990 and November 2021 was performed across Embase, Medline, Scopus and CINAHL. Studies of symptomatic or clinical endometritis were excluded. A thematic analysis across two broad themes was explored: i) diagnostic methods of SCE and ii) pathophysiology of SCE. In total, 51 bovine studies were included. Twelve studies reported on diagnostic methodology. The primary emergent theme was the use of cytology for the diagnosis of SCE. Cytological analysis has a lower sensitivity than histopathology but is less invasive and more specific than alternative techniques such as ultrasound, vaginoscopy or metabolic markers. The subthemes related to pathophysiology were identified as the type of endometritis, metabolic stress, artificial insemination, infective causes and altered cellular pathways. Despite the lack of symptoms, cellular pathways of inflammation including NF-κB, MAPK and inflammasomes were found to be activated. The key themes related to the diagnosis and pathophysiology of SCE in cows identified in this systematic review highlight potential areas for future research into human CE.</p

Assessment of associations between transition diseases and reproductive performance of dairy cows using survival analysis and decision tree algorithms

This study aimed to evaluate the associations between transition cow conditions and diseases TD with fertility in Holstein cows, and to compare analytic methods for doing so. Kaplan-Meier, Cox proportional hazard, and decision tree models were used to analyze the associations of TD with the pregnancy risk at 120 and 210 DIM from a 1-year cohort with 1946 calvings from one farm. The association between TD and fertility was evaluated as follows: 1 cows with TD whether complicated with another TD or not TD-all, versus healthy cows, and 2 cows with uncomplicated TD TD-single, versus cows with multiple TD TD+; complicated cases, versus healthy cows. The occurrence of twins, milk fever, retained placenta, metritis, ketosis, displaced abomasum, and clinical mastitis were recorded. Using Kaplan-Meier models, in primiparous cows the 120 DIM pregnancy risk was 62% (95% CI: 57-67 %) for healthy animals. This was not significantly different for TD-single (58%; 95% CI: 51-66 %) but was reduced for TD+ (45%; 95% CI: 33-60 %). Among healthy primiparous cows, 80% (95% CI: 75-84 %) were pregnant by 210 DIM, but pregnancy risk at that time was reduced for primiparous cows with TD-single (72%; 95% CI: 65-79 %) and TD+ (62%; 95% CI: 49-75 %). In healthy multiparous cows, the 120 DIM pregnancy risk was 53% (95% CI: 49-56 %), which was reduced for TD-single (36%; 95% CI: 31-42 %) and TD+ (30%; 95% CI: 24-38 %). The 210 DIM pregnancy risk for healthy multiparous cows was 70% (95% CI: 67-72 %), being higher than the 210 DIM pregnancy risk for multiparous cows with TD-single (47%; 95% CI: 42-53 %) or TD+ (46%; 95% CI: 38-54 %). Cows with TD-all presented similar pregnancy risk estimates as for TD+. Cox proportional hazards regressions provided similar magnitudes of effects as the Kaplan-Meier estimates. Survival analysis and decision tree models identified parity as the most influential variable affecting fertility. Both modeling techniques concurred that TD + had a greater effect than TD-single on the probability of pregnancy at 120 and 210 DIM. Decision trees for individual TD identified that displaced abomasum affected fertility at 120 DIM in primiparous while metritis was the most influential TD at 120 and 210 DIM for multiparous cows. The data were too sparse to assess multiple interactions in multivariable Cox proportional hazard models for individual TD. Machine learning helped to explore interactions between individual TD to study their hierarchical effect on fertility, identifying conditional relationships that merit further investigation