Search Results (33)

The uterine microbiota plays a crucial role in maintaining postpartum reproductive health in dairy cows, and its dysregulation is closely associated with uterine diseases. Vaginal discharge characteristics serve as important clinical indicators for assessing uterine status and guiding clinical decision-making. This study employed 16S rRNA gene sequencing to analyze uterine microbial diversity in cows with different discharge types. Results revealed significant microbial shifts associated with discharge severity. Notably, Caviibacter was highly enriched (up to 60.25%) in cows with mildly purulent discharge (<50%), suggesting its potential role in early-stage endometritis. In contrast, Fusobacterium and Helcococcus dominated when purulent discharge exceeded 50%, while Bacteroides, Porphyromonas, and Peptostreptococcus prevailed in cows with malodorous or discolored secretions, indicating severe inflammation. This study extends previous findings by uncovering stage-specific microbial transitions and proposing Caviibacter as a potential early biomarker of endometritis. These insights support early diagnosis and targeted interventions, contributing to improved reproductive management and sustainable dairy farming. Full article

Bovine endometritis is a common endocrine and reproductive disorder in postpartum dairy cows, closely associated with elevated systemic oxidative stress. This disease can lead to delayed uterine involution, repeated breeding failure, and significant economic losses in the dairy industry. Studies suggest that oxidative stress may contribute to the pathological progression of endometritis by regulating ECM remodeling, but the specific molecular mechanisms remain unclear. ECM homeostasis relies on the coordinated action of matrix metalloproteinases (e.g., MMP2, MMP9) and collagen (e.g., type IV collagen, COL-IV), while the TGFβ1/Smad3 signaling pathway is implicated in ECM metabolic regulation. Therefore, elucidating the regulatory mechanisms of oxidative-stress-mediated TGFβ1/Smad3 signaling on ECM remodeling is crucial for understanding the pathogenesis of endometritis. This study investigates postpartum bovine uterine tissues, comparing inflammatory cytokines (IL-1β, IL-6, TNF-α) and oxidative-stress-related factors (GPx, SOD, CAT) between healthy and endometritis groups. Additionally, the differences in ECM-remodeling-associated proteins (MMP2, MMP9, COL-IV) and TGFβ1/Smad3 pathway activity are analyzed. To further validate the mechanisms, an oxidative stress model is established in vitro by treating bovine endometrial epithelial cells (bEECs) with 200 μM H₂O₂ for 4 h, followed by the valuation of the same indicators. Furthermore, gene silencing to downregulate Smad3 expression or inhibitor-mediated suppression of TGFβ1/Smad3 pathway activity is performed to observe their regulatory effects on MMP2, MMP9, and COL-IV. The results demonstrate that oxidative-stress-mediated endometritis significantly upregulates MMP2, MMP9, and the TGFβ1/Smad3 pathway activity, while suppressing COL-IV expression. Functional genetic experiments further reveal the dual regulatory role of the TGFβ1/Smad3 pathway in ECM remodeling: (1) pathway activation promotes MMP2/MMP9 expression, accelerating COL-IV degradation; (2) Smad3 positively regulates COL-IV synthesis. These findings provide a theoretical basis for targeting the TGFβ1/Smad3 pathway to mitigate the pathological progression of endometritis. Full article

Animal production is a core sector to solve the increasing food demand worldwide, with productivity severely affected by climate change. Experts are predicting huge global productive losses in animal-derived products. Moreover, productive loss affects the economy, and the US dairy industry has reported losses of 1.5 billion dollars annually due to climate change. Beef and dairy production are based on cow reproduction and fertility is a key indicator of productivity. However, under heat stress (HS), several physiological modifications decrease cows’ fertility. Lower levels of estradiol, progesterone, and epidermal growth factor lead to undetectable ovulations, an inability to maintain the embryo and the pregnancy, or increased cortisol levels, inducing immunosuppression and, consequently, puerperal diseases delaying new pregnancies. The welfare of cows under HS, especially those raised on pasture, is a huge concern. Considering the impact of ambient-temperature-induced HS, developing strategies to improve fertility—namely through the selection of thermotolerant breeds allied to environmental management measures—can improve cattle production efficiency and reduce resource use, thereby reducing the carbon footprint. This review focuses on the effects of HS on female fertility, from parturition until the new conception, and on the role of heat shock proteins during this period. Full article

Uterine diseases in cattle are frequently linked to bacterial infections, with pathogens commonly isolated from the uterine lumen. Bovine Gammaherpesvirus Type 4 (BoGHV-4) is notably prevalent in certain regions of Argentina and is associated with uterine diseases in postpartum cattle. This study aims to evaluate the impact of platelet-rich plasma (PRP) on the gene expression related to BoGHV-4 infection in the presence of lipopolysaccharide (LPS), exploring the potential of PRP as a therapeutic alternative. The interaction between LPS and Toll-like receptor 4 (TLR4) plays a crucial role in inflammatory responses, triggering cytokine production and immune activation. Our results show that PRP modulates TLR4 and TNF-α gene expression, indicating a potential inhibitory role in inflammatory processes. Furthermore, PRP alter the temporal dynamics of BoGHV-4 replication by modulating the expression of the viral immediate–early gene (IE-2) and delaying proinflammatory cytokine responses such as IL-8. Notably, PRP enhances IFN-γ expression, which could help prevent tissue damage caused by bacterial and viral coinfection. These findings highlight the potential of PRP as an anti-inflammatory agent with therapeutic benefits in treating uterine diseases, offering an alternative to traditional antibiotic treatments. Full article

Background: In dairy cows, the stress-related cortisol level increases the susceptibility to postpartum uterine diseases. Oxidative stress is an important component of the disease process and causes morphological and functional alterations in the bovine endometrium. Selenium (Se) has an antioxidant property, and an appropriate Se supplementation is recommended to enhance bovine disease resistance. Methods and results: Here, we aimed to answer two questions: (1) how does cortisol affect the oxidative status of bovine endometrial cells; and (2) does Se supplementation protect cells from oxidative injury with a high cortisol condition? The oxidative stress of primary bovine endometrial epithelial cells (BEECs) was established by Escherichia coli lipopolysaccharide (LPS) stimulation, as marked by the increased oxidative markers and the suppressions of antioxidant indicators and Nrf2 signaling. In the absence of LPS, cortisol levels of 15 ng/mL showed a more significant antioxidative effect than cortisol levels of 5 and 30 ng/mL. In the presence of LPS, cortisol levels of 15 and 30 ng/mL elicited antioxidation, whereas 5 ng/mL of cortisol did not. Regardless of LPS stimulation, Se pretreatment of 1, 2, and 4 μM protected BEEC from oxidative stress, as evidenced by the decreased oxidative markers, increased antioxidant indices, and the activated Nrf2 signaling. With the presence of 30 ng/mL of cortisol, there was an enhanced Se antioxidant effect, which can be abolished by the block of cortisol receptor. Conclusions: Both cortisol and Se elicited antioxidant properties in BEEC through the Nrf2 pathway. In addition, the Se antioxidation was enhanced by cortisol. Full article

In the early postpartum period, dairy cows undergo significant adaptations in Ca and lipid metabolism, immune function, and inflammatory processes. Concurrent exposure to endotoxins from the uterus, gastrointestinal tract, or mammary gland increases the risk of disease and reproductive problems. Metabolic and inflammatory imbalances during this phase can have both immediate and long-term effects on reproductive health. Associations between metabolic disorders and reproductive outcomes are often confounded by immune activation and systemic inflammation. However, optimal markers, thresholds, and durations for identifying maladaptation and predicting adverse health or reproductive outcomes remain unclear. This narrative review examines key physiological changes during the transition period, including hypocalcemia, lipid mobilization, immune activation, systemic inflammation, and uterine disease. We discuss how these events may affect the dominant follicle, corpus luteum, oocyte, and uterus, potentially leading to prolonged anovulation, reduced estrus expression, impaired response to synchronization protocols, lower progesterone concentrations, and compromised fertility. Understanding these mechanisms will support the development of strategies to monitor, prevent, and mitigate the impacts of transition-related maladaptation on reproductive performance. Such advancements can enhance the health and fertility of high-producing dairy cows. Full article

Neurofibromatosis is a genetic disorder arising de novo or with an autosomal dominant transmission that typically presents either at birth or in early childhood, manifesting through distinctive clinical features such as multiple café-au-lait spots, benign tumors in the skin, bone enlargement, and deformities. This literature review aims to resume the spectrum of maternal and fetal complications encountered in pregnant women with neurofibromatosis type 1 (NF1). Thorough research was conducted on databases such as Web of Science, PubMed, Science Direct, Google Scholar, and Wiley Online Library. This review includes 48 case reports, original studies, and reviews on NF1 in pregnancy. The research on the interlink between NF1 and fertility and its influence on human-assisted reproduction techniques is limited. Preimplantation testing (by in vitro fertilization) and prenatal diagnosis (by chorionic villus sampling or amniocentesis) are available to detect affected fetuses. However, genotype–phenotype correlation is difficult to predict. Preconceptional planning and targeted investigations are crucial in understanding the extent of maternal disease. Although in some cases lesions can evolve rapidly during pregnancy, most pregnancies and births in NF1 go well with careful planning. There is a higher incidence of pheochromocytomas and pre-eclampsia, vascular rupture, and cardio-respiratory issues. Anesthesia at birth is a challenge in most cases, and before offering spinal anesthesia, imaging tests should be performed to characterize spinal lesions. General anesthesia may also be challenging when the disease affects the face, neck, upper spine, or airways. Birth-related difficulties may arise because of large neurofibromas located at the level of skin incision or birth canal; uterine atony may be expected if there are uterine lesions. Some complications can develop in postpartum, and affected women should be carefully followed even after pregnancy. Fetal risks include preterm birth (spontaneous or iatrogenic), growth restriction and developmental issues, birth complications, cardiovascular risk, and fetal/neonatal demise. Pregnancies in women with NF1 should be regarded as high-risk and followed in a multidisciplinary fashion. Careful assessment of lesions is of utmost importance before and during pregnancy for anticipating potential maternal risks and before birth to plan anesthesia and delivery. Full article

Leonurus japonicus Houtt is an exceptional medicinal herb used to treat obstetrical and gynecological diseases in traditional Chinese medicine, and it has significant effects on the treatment of dysmenorrhea and postpartum hemorrhage. This study investigated the effects of coumarins with diverse substituent groups from L. japonicus on isolated uterine smooth muscle and the preliminary mechanism of the most effective compound. Eight coumarins isolated from L. japonicus were assessed for their effects on the isolated uterine smooth muscle of nonpregnant rats in vitro. Coumarins 1 and 2 significantly promoted the contraction of rat uterine smooth muscle strips, whereas coumarins 3–5 showed remarkable relaxing effects against oxytocin (OT)-induced rat uterine smooth muscle contraction. Further mechanism investigations revealed that bergapten (coumarin 1) significantly increased the level of Ca²⁺ in uterine tissues by promoting extracellular Ca²⁺ influx and intracellular Ca²⁺ release, which were related to the activation of L-type Ca²⁺ channels and α-receptors. By contrast, osthole (coumarin 5), an α receptor antagonist, inhibited OT-induced uterine smooth muscle contraction by decreasing the level of Ca²⁺ in uterine tissues via inhibition of extracellular Ca²⁺ influx and intracellular Ca²⁺ release. This study demonstrates that the coumarins from L. japonicus are effective substances for regulating uterine smooth muscle contraction, but different coumarins with diverse substituent groups have different, even opposite effects. It can be inferred that coumarins are closely related to the efficacy of L. japonicus in the treatment of dysmenorrhea and postpartum hemorrhage. Full article

Studies in recent years indicate that reproductive tract microbial communities are crucial for shaping mammals’ health and reproductive outcomes. Following parturition, uterine bacterial contamination often occurs due to the open cervix, which may lead to postpartum uterine inflammatory diseases, especially in primiparous individuals. However, investigations into spatio-temporal microbial transitions in the reproductive tract of primigravid females remain limited. Our objective was to describe and compare the microbial community compositions in the vagina at late gestation and in the vagina and uterus at early postpartum in first-pregnancy heifers. Three swab samples were collected from 33 first-pregnancy Holstein Friesian heifers: one vaginal sample at gestation day 258 ± 4, and vaginal and uterine samples at postpartum day 7 ± 2. Each sample underwent 16S rRNA V4 region metagenetic analysis via Illumina MiSeq, with bioinformatics following Mothur MiSeq SOP. The reproductive tract bacterial communities were assigned to 1255 genus-level OTUs across 30 phyla. Dominant phyla, accounting for approximately 90% of the communities, included Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Fusobacteria. However, the results revealed distinct shifts in microbial composition between the prepartum vagina (Vag-pre), postpartum vagina (Vag-post), and postpartum uterus (Utr-post). The Vag-pre and Utr-post microbial profiles were the most distinct. The Utr-post group had lower relative abundances of Proteobacteria but higher abundances of Bacteroidetes, Fusobacteria, and Tenericutes compared to Vag-pre, while Vag-post displayed intermediate values for these phyla, suggesting a transitional profile. Additionally, the Utr-post group exhibited lower bacterial richness and diversity compared to both Vag-pre and Vag-post. The unsupervised probabilistic Dirichlet Multinomial Mixtures model identified two distinct community types: most Vag-pre samples clustered into one type and Utr-post samples into another, while Vag-post samples were distributed evenly between the two. LEfSe analysis revealed distinct microbial profiles at the genus level. Overall, specific microbial markers were associated with anatomical and temporal transitions, revealing a dynamic microbial landscape during the first pregnancy and parturition. These differences highlight the complexity of these ecosystems and open new avenues for research in reproductive biology and microbial ecology. Full article

Endometritis is a common disease in postpartum cows, characterized by delayed uterine recovery due to endometrial inflammation. Although antibiotics and hormones are commonly used, they have certain limitations. One potential alternative is using motherwort extract, specifically leonurine, which exhibits anti-inflammatory properties. However, leonurine’s exact molecular mechanism of action remains unclear. In this study, 40 mice were randomly divided into four groups: a control group, endometritis model group, LPS + leonurine group (30 mg/kg), and LPS + dexamethasone group (5 mg/kg). Transcriptomic analysis revealed that leonurine modulates multiple signaling pathways, including JAK-STAT/PI3K-Akt, and influences the expression of key genes, such as Prlr, Socs2, Col1a1, and Akt1. Furthermore, leonurine effectively reduces levels of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-1β (p < 0.01), which play a crucial role in regulating acute endometritis. Additionally, leonurine helps maintain cholesterol homeostasis and attenuates inflammation through the peroxisome proliferator-activated receptor (PPAR) signaling pathway by modulating genes such as Cyp27a1, Hmgcs1, and Scd2. These findings suggest that leonurine has a protective effect against LPS-induced endometritis and that its anti-inflammatory properties involve multiple pathways and targets, which are potentially mediated by regulating signaling pathways such as JAK-STAT/PI3K-Akt and PPAR. 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

Uterine disease in cattle impairs reproductive performance and profitability and increases antibiotic use and antimicrobial resistance. Thus, probiotics offer a promising alternative therapy. This review presents conceptual findings on the efficacy of probiotics in managing uterine diseases and fertility in cows. Probiotics containing Lactobacillus spp. and Bifidobacterium spp. individually or as composite formulations are known to improve fertility. Strategic intravaginal administration of these formulations would likely enhance uterine immunity, particularly during the postpartum period. While current findings on the benefits to uterine health are encouraging, there is still significant knowledge missing, including a lack of empirical information from large-scale field trials. This review underscores the need for evidence-based guidelines for probiotics, such as genomic selection of formulations, targeted delivery, or potential synergy with other interventions. Future research should address these gaps to maximize the potential of probiotics in managing uterine diseases and enhancing the reproductive health of dairy cattle. 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

Pregnancy in women with sickle cell disease (SCD) is a high-risk situation, especially during the third trimester of gestation and in the post-partum period, due to chronic hypoxia and vaso-occlusive phenomena occurring in the maternal–fetal microcirculation: as a result, unfavorable outcomes, such as intra-uterine growth restriction, prematurity or fetal loss are more frequent in SCD pregnancies. Therefore, there is a consensus on the need for a strict and multidisciplinary follow-up within specialized structures. Transfusion support remains the mainstay of treatment of SCD pregnancies, whereas more targeted modalities are still controversial: the benefit of prophylactic management, either by simple transfusions or by automated red blood cell exchange (aRBCX), is not unanimously recognized. We illustrate the cases of three SCD pregnant patients who underwent aRBCX procedures at our institution in different clinical scenarios. Moreover, we carried out a careful literature revision to investigate the management of pregnancy in SCD, with a particular focus on the viability of aRBCX. Our experience and the current literature support the use of aRBCX in pregnancy as a feasible and safe procedure, provided that specialized equipment and an experienced apheresis team is available. However, further research in this high-risk population, with appropriately powered prospective trials, is desirable to refine the indications and timing of aRBCX and to confirm the advantages of this approach on other transfusion modalities. 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