Search Results (36)

Hyperketonemia (HYK), defined by blood beta-hydroxybutyrate (BHB) ≥ 1.2 mmol/L, is described as a significant risk factor for cows developing postpartum (pp) diseases and impaired reproductive performance. The goal of the present study was to observe metabolic challenges in transition cows and to identify systemic markers reflecting HYK associated with lessened reproductivity. Fifty-four Simmental cows were monitored, revealing approximately 30% prevalence of HYK at the early pp period on 7, 14, or 28 days in milk (DIM). We assessed the dry matter intake, rumination time (RT), serum liver activity index, non-esterified fatty acids (NEFAs), acute phase proteins, and uterine and oviductal health. Elevated NEFA and reduced RT 14 days antepartum were a good predictor for HYK at 7 DIM. Hyperketonemia at 14 DIM resulted in higher milk yield compared with controls. We could neither detect differences in uterine health nor in reproductive key performance parameters between hyperketonemic and control cows, whereby the proportion of polymorphonuclear neutrophils in oviductal epithelia was significantly lower in hyperketonemic cows 14 DIM. We conclude that elevated concentrations of BHB in HYK 7, 14, or 28 DIM indicated energy supply to support physiological metabolic adaptations and lactation and that, in the absence of excessive inflammation during the transition period, HYK was not a risk factor for impaired fertility. Full article

Bovine endometritis negatively impairs fertility and milk production. Taurine maintains cellular integrity and exerts anti-inflammatory and antioxidant effects. However, whether taurine can treat endometritis remains unclear. This study aimed to investigate taurine’s effect on endometritis and explore its mechanism in vivo. Endometritis models were established in mice via intrauterine lipopolysaccharide (LPS) infusion, followed by 25, 50, and 100 mg/kg taurine treatment. Taurine attenuated inflammation by mitigating histopathological damage, suppressing uterine serum cytokine levels, and preserving tight-junction integrity. It ameliorated oxidative stress by reducing malondialdehyde content, restoring antioxidant activities, and recovering levels of oxidative-stress-related proteins. Apoptosis was alleviated by diminishing the apoptosis ratio and normalizing apoptosis-related proteins. 16S analysis revealed taurine restored uterine microbiota composition by reversing the changes in the abundances of Firmicutes, Bacteroidetes, Nocardioides, Ruminococcus, and Acidibacter. The abundances of Muribacter and Rodentibacter were positively correlated with inflammation. The abundances of Akkermansia and Streptococcus were negatively correlated with inflammation. RNA sequencing showed that the differentially expressed genes were mainly related to immunity. Phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)/mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) signaling pathways were indicated as pivotal mechanisms for taurine’s therapeutic efficacy against endometritis with transcriptomic profiling analysis. This study confirms that taurine alleviates LPS-induced endometritis in mice by modulating PI3K–AKT, MAPK, and NF-κB signaling pathways, indicating its potential as a therapeutic agent for bovine endometritis. Full article

Camelids are increasingly recognized as important livestock species. They are valuable sources of meat, fiber, and milk. Despite their growing popularity, many aspects of their reproductive physiology and pathology remain unclear. Their reproductive performance is reported to be low in many countries. Advances in camelid veterinary care have identified several disorders, some of which are species-specific. This article describes an approach to and the diagnosis of infertility and subfertility cases in alpacas, llamas, and camels referred to the authors over the past 35 years. Ultrasonography, endometrial cytology, and biopsy are the primary diagnostic tools for practitioners. However, laparoscopy, hysteroscopy, and cytogenetics are indicated for cases referred to theriogenologists. The incidence of congenital and acquired reproductive disorders is presented. A high incidence of congenital defects of the reproductive tract is found in South American camelids, which raises concerns about animal welfare. Acquired disorders are similar to those described in other species. Endometritis and endometrosis are major disorders contributing to infertility and early pregnancy loss. However, studies on uterine defense mechanisms and the pathogenesis of these disorders are lacking. Hydrobursitis, a common cause of infertility in dromedary camels, warrants further research. The implications of some contagious diseases (tuberculosis, campylobacteriosis, and brucellosis) in female infertility are discussed. These findings emphasize the importance of including camelid medicine in veterinary education to ensure a high standard of care for this species. Full article

Prepartum vaccination of dairy cows against newborn calf diarrhea protects calves during the first weeks of life via the colostrum. Vaccination may also induce non-specific effects (NSEs) beyond antibody production, altering the disease susceptibility and productivity of the vaccinated mother. This retrospective study analyzed herd records and on-site survey data from 73,378 dairy cows on 20 German farms using linear mixed-effects models and random forest algorithms. Management practices and milk yield showed stronger associations with outcomes than vaccination. However, the cows vaccinated with non-live vaccines had increased odds of retained placenta and metritis (OR: 1.5–1.7), as well as endometritis (OR: 3–6), and were 20–24% less likely to conceive than non-vaccinated cows. Among non-live vaccinated cows, those vaccinated 2.5–4 weeks before calving had an 8% higher non-return rate compared to those vaccinated 6–8 weeks prior. Multiparous cows receiving live vaccine components were 1.9 times more likely to conceive, compared to non-live vaccinated multiparous cows. These findings suggest potential NSE of prepartum vaccination on uterine health and fertility. However, this study’s retrospective design limits causal interpretation, and the benefits in calves may outweigh possible adverse effects. Further research should clarify the mechanisms and optimize vaccine timing and composition. Full article

Reproductive efficiency in cattle remains sub-optimal, with pregnancy rates often below 50%, despite fertilization rates approaching 100%, indicating that implantation failure and/or early embryonic loss are major limiting factors. This disparity highlights the need to understand the biological and physiological mechanisms underlying implantation failure. This review elucidates the cellular and molecular mechanisms underlying reduced pregnancy rates, with a particular focus on biological aging and fibrosis in the reproductive organs as emerging contributors to uterine dysfunction. Accumulated evidence suggests that metabolic demands associated with intensive breeding strategies aimed at maximizing meat and milk productivity may induce multiple forms of stress, including oxidative stress, metabolic stress, and inflammation, which accelerate biological aging and fibrosis in the female reproductive tract. However, the direct molecular mechanisms remain poorly characterized. We hypothesize that biological aging and fibrosis are interconnected mechanisms contributing to impaired uterine function, resulting in reduced implantation rates. By summarizing recent findings and adopting a comparative perspective, this review explores the extent to which insights from human and mouse models can be applied to cattle, considering species-specific reproductive physiology and metabolic adaptations. It explores their relevance to reproductive inefficiencies and discusses potential strategies to enhance fertility and extend bovine reproductive longevity. Full article

Olive cake was incorporated at a low inclusion rate (3.7%) into the rations of dairy cows through partial substitution of maize, and its effects on milk production, general health, and fertility traits were investigated. Multiparous purebred Holstein dairy cows (n = 148) were divided into two groups: a treated group (n = 86) and a control group (n = 62). The control ration (group C) was modified by replacing 1 kg of maize with an equal quantity of olive cake (group T). The experiment lasted from 60 days prepartum to 150 days postpartum. Electronic aids were utilized to quantify daily milk yield and detect estrus expression, while clinical and uterine examinations were performed weekly. Blood samples, uterine epithelial cells, and endometrial tissue samples were collected from a subgroup of healthy animals in both groups at specific time points. Blood samples were examined to determine the β-hydroxybutyric acid (BHBA), acute phase proteins (haptoglobin [Hpt] and serum amyloid A [SAA]), progesterone, and pregnancy-associated glycoproteins concentrations. Uterine epithelial cells were assessed for polymorphonuclear neutrophil (PMN) counts, and the expression of nine genes encoding inflammatory cytokines and immune system activation was analyzed in uterine biopsy tissue. No significant differences (p > 0.05) were observed between groups in milk yield, general morbidity, clinical endometritis, or conception rates. However, animals in group T came to estrus approximately 6 days earlier (p = 0.013) than those in group C; progesterone concentrations on day 7 of the subsequent cycle tended (p = 0.07) to be higher in group T. On day 21, BHBA concentrations were higher in group C than in group T (p < 0.05). Throughout the experiment, Hpt levels in group T were consistently lower (p < 0.001), while SAA was lower on day 7 compared to group C. From days 21 to 42 postpartum, there was a significant reduction in PMN numbers (group C p = 0.02; group T p < 0.0001), with a tendency for a greater reduction rate in group T (p = 0.08). Among the genes studied, a significant difference was revealed in the expression of the ILA1 gene, with strong correlations of gene expression in group C and weak to moderate correlations in group T. In conclusion, under the conditions of this experiment, the inclusion of olive cake into dairy cows’ rations did not affect milk production but improved certain health and fertility parameters, making olive cake a suitable alternative feedstuff for high-producing animals. Full article

Endometrial disorders, such as infertility and endometriosis, significantly impact reproductive health, thus necessitating better models to study endometrial function. Current in vitro models fail to replicate the complexity of the human endometrium throughout the entire menstrual cycle. This study aimed to assess the physiological response of human endometrial organoids (hEOs) to in vitro hormonal treatments designed to mimic the hormonal fluctuations of the menstrual cycle. Endometrial biopsies from three healthy women were used to develop hEOs, which were treated over 28 days with three hormonal stimulation strategies: (1) estrogen only (E) to mimic the proliferative phase, (2) the addition of progesterone (EP) to simulate the secretory phase, and (3) the further addition of cAMP (EPC) to enhance the secretory functions of hEOs. Gene and protein expression were analyzed using qPCR, IHC, and ELISA. The hEOs exhibited proliferation, gland formation, and appropriate expression of markers such as E-cadherin and Ki67. The hormonal treatments induced significant changes in PR, HSD17B1, PAEP, SPP1, and other genes relevant to endometrial function, closely mirroring in vivo physiological responses. The prominent changes were observed in EPC-treated hEOs (week 4) with significantly high expression of uterine milk components such as glycodelin (PAEP) and osteopontin (SPP1), reflecting mid- to late-secretory phase physiology. This model successfully recapitulates human menstrual cycle dynamics and offers a promising platform for studying endometrial disorders and advancing personalized treatments in gynecology. Full article

The left displacement of the abomasum (LDA) is a common condition in dairy cows that can significantly impact their welfare, productivity, and fertility. This study was carried out in Greek dairy farms over a period of 3 years. To ensure early detection, the farmers were trained to accurately identify the disease. The reproductive performance and milk production of 306 cows was assessed by considering the time to the first estrus, the calving-to-conception interval, and the number of artificial inseminations required for the establishment of pregnancy. Uterine health status, the timing of disease diagnosis, and the season of the year were also evaluated. In a separate study, the outcomes of 26 cases where cows suffered LDA and underwent surgical treatment with a delay of at least one week from disease onset, were compared to those of cases promptly treated. The results indicate that even early identification and treatment of LDA affects fertility and milk yield; these impacts worsen with the co-existence of uterine infections of affected. However, in late-treated cases, all reproductive and production indices show significant deterioration. Our findings suggest that timely diagnosis of the disease, preferably by the farmer, ensures minimal losses in cows affected by LDA. Full article

Oxytocin, a significant pleiotropic neuropeptide, regulates psychological stress adaptation and social communication, as well as peripheral actions, such as uterine contraction and milk ejection. Recently, a Japanese Kampo medicine called Kamikihito (KKT) has been reported to stimulate oxytocin neurons to induce oxytocin secretion. Two-pore-domain potassium channels (K2P) regulate the resting potential of excitable cells, and their inhibition results in accelerated depolarization that elicits neuronal and endocrine cell activation. We assessed the effects of KKT and 14 of its components on a specific K2P, the potassium channel subfamily K member 2 (TREK-1), which is predominantly expressed in oxytocin neurons in the central nervous system (CNS). KKT inhibited the activity of TREK-1 induced via the channel activator ML335. Six of the 14 components of KKT inhibited TREK-1 activity. Additionally, we identified that 22 of the 41 compounds in the six components exhibited TREK-1 inhibitory effects. In summary, several compounds included in KKT partially activated oxytocin neurons by inhibiting TREK-1. The pharmacological effects of KKT, including antistress effects, may be partially mediated through the oxytocin pathway. Full article

Mineral metabolism, in particular Ca, and to a lesser extent phosphorus (P) and magnesium (Mg), is altered with the onset of lactation because of extensive irreversible loss to synthesize colostrum and milk. The transient reduction in the concentration of Ca in blood, particularly when it lasts days, increases the risk of mineral-related disorders such as hypocalcemia and, to a lesser extent, hypophosphatemia. Although the incidence of clinical hypocalcemia can be reduced by prepartum dietary interventions, subclinical hypocalcemia remains prevalent, affecting up to 60% of the dairy cows in the first 3 d postpartum. More importantly, strong associations exist between hypocalcemia and increased susceptibility to other peripartum diseases and impaired reproductive performance. Mechanistic experiments have demonstrated the role of Ca on innate immune response in dairy cows, which presumably predisposes them to other diseases. Hypocalcemia is not related to inadequate Ca intake as prepartum diets marginal to deficient in Ca reduce the risk of the disease. Therefore, the understanding of how Ca homeostasis is regulated, in particular how calciotropic hormones such as parathyroid hormone and 1,25-dihydroxyvitamin D₃, affect blood Ca concentrations, gastrointestinal Ca absorption, bone remodeling, and renal excretion of Ca become critical to develop novel strategies to prevent mineral imbalances either by nutritional or pharmacological interventions. A common method to reduce the risk of hypocalcemia is the manipulation of the prepartum dietary cation-anion difference. Feeding acidogenic diets not only improves Ca homeostasis and reduces hypocalcemia, but also reduces the risk of uterine diseases and improves productive performance. Feeding diets that induce a negative Ca balance in the last weeks of gestation also reduce the risk of clinical hypocalcemia, and recent work shows that the incorporation of mineral sequestering agents, presumably by reducing the absorption of P and Ca prepartum, increases blood Ca at calving, although benefits to production and health remain to be shown. Alternative strategies to minimize subclinical hypocalcemia with the use of vitamin D metabolites either fed prepartum or as a pharmacological agent administered immediately after calving have shown promising results in reducing hypocalcemia and altering immune cell function, which might prove efficacious to prevent diseases in early lactation. This review summarizes the current understanding of Ca homeostasis around parturition, the limited knowledge of the exact mechanisms for gastrointestinal Ca absorption in bovine, the implications of hypocalcemia on the health of dairy cows, and discusses the methods to minimize the risk of hypocalcemia and their impacts on productive performance and health in dairy cows. Full article

The metritis complex (MC), a group of post-partum uterine diseases, is associated with increased treatment costs and reduced milk yield and fertility. The goal of this study was to identify genetic variants, genes, or genomic regions that modulate MC disease. A genome-wide association study was performed using a single-locus mixed linear model of 1967 genotypes (624,460 SNPs) and metritis complex records. Then, in-silico functional analyses were performed to detect biological mechanisms and pathways associated with the development of MC. The ATP8A2, COX16, AMN, and TRAF3 genes, located on chromosomes 12, 10, and 21, were associated with MC at p ≤ 0.0001. These genes are involved in the regulation of cholesterol metabolism in the stromal tissue of the uterus, which can be directly associated with the mode of transmission for pathogens causing the metritis complex. The modulation of cholesterol abundance alters the efficiency of virulence factors and may affect the susceptibility of the host to infection. The SIPA1L1, DEPDC5, and RNF122 genes were also significantly associated with MC at p ≤ 0.0001 and are involved in the PI3k-Akt pathway, responsible for activating the autophagic processes. Thus, the dysregulation of these genes allows for unhindered bacterial invasion, replication, and survival within the endometrium. Full article

This manuscript aims to report the clinical and laboratory diagnosis of puerperal metritis (PM) in a dairy cow, caused by H. somni as a unique pathogen. The cow showed signs of systemic illness, including a sudden drop in milk production, a rectal temperature of 40.4 °C, tachypnea, dehydration, and completely fluid, brown, and fetid uterine discharge. Pure cultures of H. somni were identified and submitted to the Kirby–Bauer disc diffusion method for antibiotic sensitivity. The study showed that H. somni was resistant to tetracyclines and cephalosporins (Ceftiofur), antibiotics commonly used to treat uterine infections in dairy cows. To the authors’ knowledge, this case describes for the first time PM caused by H. somni as a primary pathogen. Our results should lead to the inclusion of H. somni as a primary pathogen of metritis in laboratory diagnoses on a routine basis, which, in turn, may help to elucidate the incidence of H. somni as a causative agent of uterine infections in cows. If the incidence of H. somni is remarkably high or frequent, researchers could consider the use of commercial vaccines nowadays destined for the prevention of bovine respiratory disease and which could perhaps be effective in the prevention of reproductive pathology caused by H. somni. Full article

Caesarean section birth (CS) accounts for 38% of Australian births and is known to negatively impact breastfeeding exclusivity and duration. Comparison of breastfeeding outcomes between elective (ELUSCS) and non-elective lower uterine segment caesarean section (NELUSCS) births is needed to inform clinical care. Secondary analysis was performed on data from Australian women who had birthed by CS within the previous 12 months and completed an anonymous online questionnaire. Women responded to items relating to CS birth type and feeding methods immediately post birth, during the hospital stay and in the first 2 weeks at home. Self-reported pain at those time points was rated using a scale of 0–10 with 0 indicating no pain and 10 indicating severe pain. Associations between CS birth type, pain scores and feeding methods were determined, and breastfeeding prevalence at the time of survey completion examined. Our sample consisted of 851 women at 5 ± 3.5 months postpartum, of which 435 (51.1%) were primiparous and 362 (42%) had a NELUSCS birth. Infants born by NELUSCS were more likely to receive formula (37.1% vs. 28.8% ELUSCS, p = 0.024) and less likely to be breastfed (78.6% vs. 85.9% ELUSCS, p = 0.022) during the hospital stay. During the 2 weeks after discharge, women who birthed by NELUSCS had higher mean pain scores (6.5 vs. 4.6 ELUSCS, p < 0.001). Few women expressed and fed their milk in the weeks after discharge, with higher rates seen after NELUSCS (7.7% vs. 3.5%, p = 0.017). Breastfeeding status at study completion was not associated with CS birth type (19.6% ELUSCS vs. 19% NELUSCS, p = 0.99). The study findings indicate that Australian women who give birth by NELUSCS are more likely to experience breastfeeding challenges, with higher rates of infant formula supplementation and a more painful recovery in the days and weeks after birth. In light of the higher postpartum pain scores and lower rates of exclusive breastfeeding, women who birth by NELUSCS need additional postpartum support. Full article

The objective of this study was to identify alterations in the vaginal discharge (VD) metabolome and potential biomarkers to predict metritis development and a cure in dairy cows. This prospective cohort study was conducted on two dairies located in CA and TX. Vaginal discharge was evaluated and collected using the Metricheck^® device. Cows were examined for metritis at 4, 7, and 9 days in milk (DIM). Cows with a fetid, watery, and reddish-brown uterine discharge were classified as having metritis and randomized to receive ceftiofur (n = 10) or remain untreated (n = 7). A cure was defined as the absence of a fetid, watery, reddish-brown uterine discharge at 14 d after enrollment. Vaginal discharge samples were collected from 86 cows within 6 h after parturition, at 4 and 7 DIM, at metritis diagnosis, and at 4 and 7 days after metritis diagnosis. Cows with metritis (MET; n = 17) were paired with counterparts without metritis (HTH) of a similar DIM and parity (n = 34). The uterine metabolome was evaluated using untargeted gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). Metabolomic data were analyzed using the MetaboAnalyst 5.0. Data were log-transformed and auto-scaled for normalization. Univariate analyses, including the fold-change, were performed to identify the metabolites linked to metritis development and its cure and principal component analysis and partial least squares discriminant analysis were performed to explain metabolite variance between animals developing or not developing metritis and being cured or not being cured of metritis. Comparing HTH with MET cows at calving, 12 metabolites were upregulated, and one was downregulated. At four and seven DIM, 51 and 74 metabolites, respectively, were altered between MET and HTH cows. After metritis development, three and five metabolites were upregulated in cows that were cured and in cows that received treatment and were cured, respectively. In all scenarios, the metabolites lignoceric, malic, and maleic acids, ornithine, and hypotaurine, which are associated with arginine/aminoacyl-tRNA biosynthesis and taurine/purine metabolism, were upregulated in HTH cows. Metritis was associated with changes in the uterine metabolome. Cows not being cured of metritis had changes in the uterus metabolome independent of receiving ceftiofur or remaining untreated. Metabolome analysis may be an important tool to understand the vaginal discharge changes during postpartum and the dynamics of metritis development and cures and help to identify biomarkers to predict metritis being cured. Full article

Metritis is a postpartum uterine disease with greater incidence in primiparous than in multiparous cows. In primiparous cows, the impact on production and health is lessened, presumably due to a superior immune response. Here, we tested whether an in vivo model of clinical metritis induction developed for postpartum multiparous Holstein cows would produce similar results in primiparous cows. Thirty-six cows were randomly assigned to one of three groups and received intrauterine infusion within 24 h of parturition. The controls were infused with sterile saline; the low-dose group received a bacterial cocktail containing 10³ cfu of Escherichia coli, Trueperella pyogenes, and Fusobacterium necrophorum; and the high-dose group were infused with 10⁶ cfu of the same cocktail. Production, health traits, and the vaginal discharge culture were assessed daily, from enrollment until 14 d in milk. Clinical metritis occurred in 64% of high-dose cows, 33% of the controls, and 42% of low-dose cows, with no significant difference of incidence between groups. However, when accounting by time, high-dose cows had a 2.7 times greater hazard of metritis compared with the controls. The bacterial challenge affected milk production and dry matter intake tended to decrease. In the high-dose group, a greater growth of F. necrophorum in the selective medium was also observed, suggesting an association with metritis. Therefore, this study suggests intrauterine inoculation with 10⁶ cfu of this bacterial cocktail elicits physical and clinical outcomes consistent with clinical metritis. Full article