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Objective To decrease the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the Mount Sinai Hospital's obstetric service, additional contact and respiratory precautions for patients and staff were implemented. Patients were allowed only one support person, SARS-CoV-2 tested on admission, and required to mask during hospitalization. Staff were required to wear masks and eye shields, gloves for all patient care, and gowns for care with SARS-CoV-2-infected patients. This study determined if the risk of endometritis/intra-amniotic infection (IAI) changed under the new pandemic precautions. Study Design A single-center, historical cohort study via electronic medical record review compared singleton deliveries among patients who labored during the "pandemic period" (from March 1 through May 31, 2020) with those who labored during the "prepandemic period" (March 1 through May 31, 2019) to determine if the risk of endometritis/IAI differed. The analysis was done using logistic regression with inverse probability of treatment weighting (IPTW) to adjust for possible differences in obstetric practice and patient population between the two periods. Results Four percent (53/1,318) of patients in the pandemic period and 5.1% (82/1,596) of patients in the prepandemic period were diagnosed with endometritis/IAI (p = 0.15). Compared with patients who delivered in the prepandemic period, those who delivered during the pandemic period had a higher body mass index at delivery (median: 28.36 [interquartile range, IQR: 25.70, 32.07] vs. 28.00 [IQR: 25.23, 31.50], p = 0.01) and experienced fewer digital exams (median: 4 [range: 1, 10] vs. 4 (range: 1, 19], p = 0.004), a practice not included in the SARS-CoV-2 prevention strategy. In multivariable logistic regression with IPTW adjusting for risk factors for endometritis/IAI, period of delivery was not associated with endometritis/IAI (odds ratio = 0.76, 95% confidence interval [0.52, 1.11], p = 0.15). Conclusion The use of respiratory and contact precautions to limit the spread of SARS-CoV-2 was not associated with risk of endometritis/IAI. Key Points Pandemic infection control precautions were not associated with a decrease in endometritis/IAIs. The early months of the pandemic were associated with the performance of fewer digital cervical exams. The early months of the pandemic were associated with a higher BMI at delivery. [ABSTRACT FROM AUTHOR]

Chlamydia abortus is a reported cause of infertility and endometritis in sheep, cattle, and pigs; however, the association between uterine disease and C. abortus is poorly understood in horses. Recently, a high prevalence of C. abortus in equine aborted chorioallantoises was reported in horses in western Canada. Based on this high prevalence, investigation into the effects of C. abortus on infertility and endometritis in western Canadian mares is prudent. We examined 98 formalin-fixed, paraffin-embedded endometrial biopsies from western Canada submitted between 2014 and 2022 using a Chlamydia -specific 16S rRNA PCR test; 40 samples tested positive for Chlamydia on PCR, and 28 were sequenced as C. abortus. The C. abortus –positive cases were primarily associated with a history of failure to conceive, early embryonic loss, or abortion. Our findings suggest that C. abortus may be a cause of conception failure and abortion in horses in western Canada. [ABSTRACT FROM AUTHOR]

Endometritis and metritis are common reproductive diseases in domestic animals, causing a reduction in reproductive performance and economic losses. A previous study revealed the alterations in the transcriptome of the inflamed porcine endometrium. Data on molecular signatures in the myometrium under inflammatory conditions are limited. The current study analyzed the transcriptomic profile of porcine myometrium after intrauterine Escherichia coli (E. coli) administration. On day 3 of the estrous cycle (Day 0 of the study), 50 ml of either saline (group CON, n = 7) or E. coli suspension (109 colony-forming units/ml, group E. coli, n = 5) were injected into each uterine horn. After eight days, the gilts were euthanized, and the uteri were removed for further analysis. In the myometrium of the CON group versus the E. coli group, microarray analysis revealed 167 differentially expressed genes (DEGs, 78 up- and 89 down-regulated). After intrauterine E. coli administration, among the DEGs of the inflammatory response set, the highest expressed were mRNA for CXCL6, S100A8, S100A12, SLC11A1, S100A9 , CCL15, CCR1, CD163, THBS1 and SOCS3, while the most suppressed was mRNA expression for FFAR4, KL, SLC7A2 and MOAB. Furthermore, a comparison of the present results on myometrial transcriptome with the authors' earlier published data on the endometrial transcriptome shows the partial differences in mRNA expression between both layers after intrauterine E. coli injections. This study, for the first time, presents changes in the transcriptome of porcine myometrium after intrauterine E. coli administration, which may be important for myometrial homeostasis and functions and, as a result, for the uterine inflammation course. Data provide a valuable resource for further studies on genes and pathways regulating uterine inflammation and functions. • E.coli-injected intrauterine increases CXCL6, S100A8, S100A12 genes in myometrium. • E.coli-injected intrauterine down-regulates IGSF5, FFAR4, KL genes in myometrium. • The most altered genes in myometrium enrich pathway: role of IL-17A in psoriasis. • LPS is a top upstream regulator for differentially expressed genes in myometrium. [ABSTRACT FROM AUTHOR]

Endometritis is mostly caused by childbirth or postpartum uterine infection. It is one of the important reasons leading to female infertility. Caffeic acid (CA) and its derivatives are widely found in some foods and traditional Chinese medicine, and have biological activities such as antioxidant, free radical scavenging, anti‐inflammatory, and anti‐infection. In this study, we aimed to explore the effect of CA on Staphylococcus aureus‐induced endometritis. The contents of TNF‐α and IL‐1β were detected by ELISA in S. aureus‐induced endometritis model. Western blot assay was used to detect the expression of AMPKα/mTOR/HIF‐1α pathway related proteins and GPX4 expression. In addition, the concentrations of MDA, GSH, and iron were tested by the assay kits. Compared with the model group, CA treatment significantly alleviated S. aureus‐induced uterine injury, MPO activity, the contents of inflammatory factors TNF‐α and IL‐1β, and NF‐κB activation. Meanwhile, CA significantly inhibited S. aureus‐induced ferroptosis, as confirmed by decreased MDA and iron concentration and up‐regulated GPX4 expression and GSH level. Furthermore, CA attenuated S. aureus‐induced HIF‐1α and phosphorylated mTOR expression and increased phosphorylated AMPK expression. In conclusion, CA inhibits inflammation and ferroptosis by regulating AMPKα/mTOR/HIF‐1α signalling pathway to alleviate S. aureus‐induced endometritis in mice. [ABSTRACT FROM AUTHOR]

Background and Aim: Postpartum reproductive tract infections pose significant challenges to dairy farms, leading to economic losses due to reduced fertility associated with uterine inflammation. In veterinary practice, numerous research groups have explored the underlying causes of subfertility in cows, including surveying endemic viral infections related to endometritis in local areas. This study investigated bovine herpesvirus 4 (BoHV-4) infection in Thai dairy herds and assessed its impact on endometritis and subsequent reproductive outcomes. Materials and Methods: The present study analyzed BoHV-4 DNA in various samples, including milk, blood, and endometrial tissue, from 44 Holstein-Friesian cows 21-47 days postpartum across five dairy herds in Central Thailand. BoHV-4 glycoprotein B and thymidine kinase DNA sequences were detected using the polymerase chain reaction (PCR) and nested PCR, with sequence comparisons made to GenBank data for phylogenetic analysis. The endometritis status was diagnosed through vaginal mucus examination and endometrial cytology, with reproductive performance monitored up to the subsequent calving. Results: BoHV-4 DNA was identified in blood and endometrial tissues (15.91%) but not in milk samples. Phylogenetic analysis revealed that the local BoHV-4 strains are similar to those identified in Brazil and Japan. Notably, the presence of BoHV-4 was correlated with reduced postpartum reproductive performance, particularly extending the interval from calving to the first service. Conclusion: Our findings underscore the importance of integrating BoHV-4 genomic surveys and uterine health assessments to refine reproductive management strategies within the dairy industry. [ABSTRACT FROM AUTHOR]

Endometritis is a common inflammatory condition of the uterine endometrial lining that primarily affects perinatal dairy animals and causes significant economic losses in agriculture. It is usually triggered by pathogenic bacteria and is associated with chronic postpartum reproductive tract infections. Bacterial lipopolysaccharides (LPSs) are known to increase levels of reactive oxygen species (ROS), leading to oxidative stress and inflammation through the activation of the NF-κB signaling pathway and the inhibition of Nrf2 nuclear translocation, which regulates antioxidant response elements (AREs). The effectiveness of the conventional management strategy involving antibiotics is decreasing due to resistance and residual concerns. This review explores the potential therapeutic benefits of targeting the Nrf2/Kelch-like ECH-associated protein 1 (Keap1)/NF-κB signaling pathway to alleviate LPS-induced endometritis. We discuss recent advancements in veterinary medicine that utilize exogenous antioxidants to modulate these pathways, thereby reducing oxidative stress and inflammatory responses in endometrial cells. This review highlights the efficacy of several bioactive compounds that enhance Nrf2 signaling and suppress NF-κB activation, offering protective effects against oxidative damage and inflammation. By examining various in vitro studies, this review emphasizes the emerging role of these signaling pathways in developing new therapeutic strategies that could potentially replace or supplement traditional treatments and mitigate the economic impacts of endometritis in livestock. [ABSTRACT FROM AUTHOR]

Summary Fungal endometritis and placentitis have been reported as a rare but important cause of infertility in the mare. There are no reported clinical cases of fungal endometritis causing embryonic loss in the mare. This case report aims to highlight the potential of fungal endometritis as an aetiological agent in embryonic loss in the mare; an incidental diagnosis of a case of fungal endometritis and embryonic loss while undertaking routine pregnancy assessments in a Standardbred mare. After a positive pregnancy diagnosis after 13 days post‐ovulation, a mare was diagnosed with endometritis and pregnancy loss associated with the growth of an unusual fungus, likely of the Acremonium spp., 28 days post‐ovulation. While fungal embryonic loss is rare, it should be considered a potential reason for pregnancy wastage in the mare. [ABSTRACT FROM AUTHOR]

• CD38 combined with CD138 in chronic endometritis improves the diagnostic accuracy. • The prevalence of chronic endometritis is nearly one-third in the infertile population. • Reproductive outcomes were improved in patients with chronic subtrotritis after combined laparoscopic surgery. To investigate the prevalence of chronic endometritis (CE) in infertile patients and whether it affects spontaneous pregnancy after reproductive surgery in infertile patients. In this study, we collected clinical information on infertility patients who underwent reproductive surgery at the Reproductive Medicine Centre of the Second Hospital of Lanzhou University from 2021.1 to 2022.8. All patients underwent laparoscopic and hysteroscopic surgery. Tubal lubrication was performed concurrently with endometrial sample collection and pathological examination. The specimens were immunohistochemically stained with CD38 and CD138, and those who tested positive at the same time were diagnosed with chronic endometritis. As of 2023.9, the patients were followed up by telephone to determine whether chronic endometritis impacted postoperative pregnancy. A total of 81 patients were finally included in the study. Of these, 25 were in the chronic endometritis group, and 56 were in the non-chronic endometritis group. There were no appreciable differences between the two groups' demographic statistics. Furthermore, neither the bilateral appendages nor the uterus's intraoperative conditions showed a statistically significant difference. Patients in the chronic endometritis group had a longer time to conception from the time of surgery (7 (6.00–11.75) vs. 10 (6.50–16.00), p = 0.467) and a lower rate of spontaneous pregnancies (8/25 = 32.00 % vs. 28/55 = 50.00 %, p = 0.132) than patients with non-chronic endometritis. Among the patients who had successful spontaneous pregnancies after surgery, approximately 77.14 % had live births and 22.86 % had miscarriages, and the live birth rate between the two groups was not significantly different. (21/28 = 75.00 % vs 7/8 = 87.50 %, p = 0.651) Chronic endometritis affects approximately 31.82% of infertile patients, and following reproductive surgery, it has no discernible impact on spontaneous pregnancy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the utility of cervical cultures in the diagnosis and management of postpartum endometritis. Methods: A retrospective study was conducted on 1069 cervical cultures collected from postpartum women with suspected endometritis between 2011 and 2021. Patient demographics, obstetric history, clinical parameters, and culture results were analyzed. Microorganisms were categorized into five groups based on species and virulence. Statistical analysis was performed to identify associations between risk factors, pathogens, and disease severity. Results: The positivity rate for distinct microorganisms in cervical cultures was 33.1%. Escherichia coli (10.8%) and Group B Streptococcus (7.5%) were the most common isolates. Prolonged labor duration and prolonged rupture of membranes were associated with Enterobacterales infections. Elevated white blood cell count was linked to Enterobacterales and beta-hemolytic Streptococci, while the former were also associated with higher rate of postpartum clinic visit. No significant differences in disease severity were found between other microorganism groups. Conclusion: The study suggests that while cervical cultures can identify potential pathogens in postpartum endometritis, their clinical utility is questionable due to the polymicrobial nature of the disease and the isolation of commensal microorganisms. The lack of significant differences in disease severity across various microorganism groups raises questions regarding the contribution of distinct bacterial identification in endometritis management. [ABSTRACT FROM AUTHOR]

Prostaglandins have many roles in the equine reproductive tract, including but not limited to luteolysis, luteal support, ovulation, transport through the uterine tube, uterine contraction, embryonic mobility, inflammation, and fibrosis. Altered secretion of inflammatory proteins are likely to disrupt the balance of endometrial function and could impair fertility. Our overall goal was to measure the expression of several prostaglandin- and inflammation-related genes in mares with different degrees of endometrial histological changes. Our hypothesis was that mares with neutrophilic and lymphocytic plasmocytic inflammation, fibrosis, or different biopsy grades would have altered concentrations of prostaglandin E2 (PGE2) and F2α (PGF2α), as well as altered expression of inflammation- and prostaglandin-related genes, compared to mares with minimal to no histological changes on biopsy evaluation. Forty-five endometrial biopsies from estrous mares were assessed by a reproductive pathologist for the degree of neutrophilic inflammation, lymphocytic and plasmocytic inflammation, and fibrosis, and a biopsy grade was assigned based on the Kenney-Doig system. A low-volume uterine lavage was collected from a subset of twenty-six mares prior to biopsy collection and was used to measure PGE2 and PGF2α concentrations via ELISA. Total RNA was extracted from biopsies and mRNA expression was evaluated for twenty-five genes of interest. A restricted maximum likelihood linear model was used to compare differences of mRNA expression, with a statistical significance set at P < 0.05. There was no difference in the abundance of PGE2 or PGF2α between any of the variables tested. Mares with endometrial biopsy grade I had lower expression of NF-kB, PTGS1 and HPGD compared to grade IIA or IIB (P < 0.05). Mares with neutrophilic inflammation had decreased expression of NF-kB, PTGS1, PTGER4, CBR1, mPGES2 and PTGIS compared to mares without inflammation. Mares with mild or minimal endometrial fibrosis had increased expression of mPGES2 and PTGIS , compared to mares with moderate endometrial fibrosis. In conclusion, several genes were identified to be differentially expressed in mares with histological changes compared to mares with no to minimal histological changes. The presence of inflammation and fibrosis may alter the concentration of prostaglandins in endometrial tissue, which could impair many of the uterine reproductive and immune functions during estrus, affecting early embryo survival. • Prostaglandins were differentially expressed based on histological assessment. • Prostaglandin expression was increased in IIA and IIB endometrial biopsies. • mPGES2 and PTGIS relative expression were decreased with moderate fibrosis. • Endometrial biopsies with inflammation had decreased prostaglandin expression. [ABSTRACT FROM AUTHOR]

Defining the optimal therapy for endometritis remains a significant challenge for clinicians. Given the public health threat posed by antibiotic resistance and the inconclusiveness of traditional therapies, regenerative medicine has been proposed as an alternative. The objective of this study was to conduct a comprehensive systematic review and meta-analysis, to investigate the efficacy of regenerative medicine products in the treatment of both post-breeding persistent and chronic degenerative endometritis (PBIE/CDE) in mares, following the PRISMA guidelines. This research could be a comprehensive scientific reference for determining appropriate treatments and clinical strategies. All studies exploring the use of regenerative medicine therapies (i.e., plasma products, autologous conditioned serum, mesenchymal stem cells MSCs, and MSC derivatives) in the treatment of PBIE/CDE were included, regardless of the specific protocol used, the evaluated outcomes, or the diagnostic method employed. Two authors independently gathered data and evaluated the risk of bias for each study. Treatment effects were assessed using risk ratios for dichotomous data, accompanied by 95 % confidence intervals. Data were aggregated utilizing the fixed-effects model. The quality of evidence for each outcome was evaluated using GRADE criteria. Eighteen studies were included in the systematic review, while fifteen trials were included in the meta-analysis. A sub-meta-analysis was conducted separately on platelet-derived products, as well as on MSCs and their derivatives. The results demonstrated an overall positive effect of regenerative therapies in treating PBIE/CDE, particularly those involving MSCs and their derivatives. The positive outcomes include an anti-inflammatory effect, characterized by reduced intrauterine fluid accumulation, neutrophils, and cytokine concentrations. Additionally, improvements in pregnancy, foaling, and embryo recovery rates have been observed in some cases. Despite the limited number of randomized controlled studies and the high variability among protocols, including the timing of treatment, type, and volume of products used, the use of regenerative products, especially MSCs and their derivatives, has promising results in terms of both efficacy and safety for treating PBIE/CDE in mares. • Regenerative therapies can serve as an alternative to antibiotics for endometritis. • Regenerative therapies demonstrated anti-inflammatory effects on the endometrium. • Regenerative therapies have shown effectiveness in treating endometritis in mares. • Treatment with mesenchymal stem cells and derivatives resulted in satisfactory outcomes. [ABSTRACT FROM AUTHOR]

Equine endometritis is one of the main causes of subfertility in the mare. Unraveling the molecular mechanisms involved in this condition and pinpointing proteins with biomarker potential could be crucial in both diagnosing and treating this condition. This study aimed to identify the endometritis-induced changes in the endometrial proteome in mares and to elucidate potential biological processes in which these proteins may be involved. Secondly, biomarkers related to bacterial endometritis (BE) in mares were identified. Uterine lavage fluid samples were collected from 28 mares (14 healthy: negative cytology and culture, and no clinical signs and 14 mares with endometritis: positive cytology and culture, in addition to clinical signs). Proteomic analysis was performed with a UHPLC-MS/MS system and bioinformatic analysis was carried out using Qlucore Omics Explorer. Gene Ontology enrichment and pathway analysis (PANTHER and KEGG) of the uterine proteome were performed to identify active biological pathways in enriched proteins from each group. Quantitative analysis revealed 38 proteins differentially abundant in endometritis mares when compared to healthy mares (fold changes >4.25, and q-value = 0.002). The proteins upregulated in the secretome of mares with BE were involved in biological processes related to the generation of energy and REDOX regulation and to the defense response to bacterium. A total of 24 biomarkers for BE were identified using the biomarker workbench algorithm. Some of the proteins identified were related to the innate immune system such as isoforms of histones H2A and H2B involvement in neutrophil extracellular trap (NET) formation, complement C3a, or gelsolin and profilin, two actin-binding proteins which are essential for dynamic remodeling of the actin cytoskeleton during cell migration. The other group of biomarkers were three known antimicrobial peptides (lysosome, equine cathelicidin 2 and myeloperoxidase (MPO)) and two uncharacterized proteins with a high homology with cathelicidin families. Findings in this study provide the first evidence that innate immune cells in the equine endometrium undergo reprogramming of metabolic pathways similar to the Warburg effect during activation. In addition, biomarkers of BE in uterine fluid of mares including the new proteins identified, as well as other antimicrobial peptides already known, offer future lines of research for alternative treatments to antibiotics. • Mares with bacterial endometritis exhibited a significantly higher relative abundance of endometrial proteins compared to clinically healthy mares. • The proteins upregulated in the secretome of mares with bacterial endometritis were involved in biological processes related to the generation of energy and REDOX regulation and to the defense response to bacterium (neutrophil extracellular trap (NET) formation pathway). • A total of 24 biomarkers for bacterial endometritis were identified. Some of the proteins identified were related to the innate immune system such as isoforms of histones H2A and H2B, complement C3a, or gelsolin and profilin. The other group of biomarkers were three known antimicrobial peptides (lysosome, equine cathelicidin 2 and MPO) and two uncharacterized proteins with a high homology with cathelicidin families. [ABSTRACT FROM AUTHOR]

Background: The endometrium holds a crucial role in reproduction by supporting blastocyst adhesion, cytotrophoblast invasion and fetal development. Among the various uterine disorders, endometritis, particularly chronic endometritis (CE), has gained attention due to its association with adverse reproductive outcomes (recurrent pregnancy loss (RPL), recurrent implantation failure (RIF), and infertility). The association between CE and adverse reproductive outcomes stresses the necessity for comprehensive diagnostic and therapeutic strategies to optimize fertility outcomes and support individuals in their journey towards parenthood. Aim: To explore the relationship between CE and reproductive disorders. Methods: Following PRISMA guidelines, a systematic review and meta-analysis using published data from 1990 to 2024 were carried out. Results: A population of 1,038 women was included. Regarding CE-infertility association, a positive correlation was found, with 19.46% CE rate in infertile women compared to 7.7% in controls (OR: 2.96, 95% CI 1.53-5.72, p 0.001). No significant association was observed between RIF and CE (OR: 1.10, 95% CI 0.26-4.61, p 0.90), CE rates in both groups were relatively comparable, with 6.35% in women with RIF and 5.8% in controls. On the opposite, a strong association between CE and RPL was found, reporting a CE rate of 37.6% in RPL cases compared to 16.4% in controls (OR: 3.59, 95% CI 2.46-5.24, p < 0.00001). Conclusions: CE appears to be associated to infertility and RPL, while no significant association was noted in cases of RIF. [ABSTRACT FROM AUTHOR]

Background: Endometritis seriously affects maternal reproductive health and fertility. Natural compounds have the characteristics of high efficiency and low residue in disease treatment. We aimed to discover and reveal the pharmacological effects of naringin, which is widely present in food and plants, on endometritis. Methods: Based on network pharmacology, the potential targets and pathways of naringin's actions on endometritis were predicted. Animal in vivo experiments were conducted to examine the inflammatory response of lipopolysaccharides (LPSs) in uterine tissue and the therapeutic effect of naringin. An in vitro primary bovine endometrial epithelial cell inflammation and drug treatment model was constructed. The production of reactive oxygen species (ROS) was measured using DCFH-DA, and the effect of naringin on LPS-induced endometritis was evaluated using HE staining, real-time quantitative PCR, Western blot, and immunofluorescence staining methods. Results: Naringin alleviated LPS-induced inflammatory injury and oxidative stress in the endometrium of mice and bovine endometrial epithelial cells (bEECs). Furthermore, in vitro studies were carried out to reveal the potential anti- inflammatory mechanisms of naringin based on network pharmacology. We found that naringin significantly inhibited LPS-stimulated endoplasmic reticulum stress (ERS)-related gene and protein expression, thus reducing the unfolded protein response (UPR). Furthermore, treatment of naringin attenuated the autophagic flux induced by ERS. In a further study, we observed that PI3K/AKT pathway inhibitors or ERS inducers partially reverse naringin's inhibition of autophagy and cell apoptosis. Conclusion: It is demonstrated that naringin suppresses autophagy by directly inhibiting the ERS-PI3K/AKT axis and exerting anti-inflammatory and antioxidant effects in endometritis. These findings provide novel insights into the pathogenesis of endometritis, highlighting potential therapeutic targets of traditional herbs and compounds. [ABSTRACT FROM AUTHOR]

Background and Aim: Postpartum uterine disease, such as endometritis, is widespread in highly productive dairy cows, leading to fertility problems and economic losses. Despite existing diagnostic methods, early and effective detection of uterine infections remains problematic due to the subclinical nature of some conditions. This study aimed to develop and evaluate a rapid diagnostic test for endometritis in cows on different days postpartum (PP). Materials and Methods: The study was carried out on dairy Holstein–Friesian cows (n = 121) kept on farms in northern Kazakhstan. The study included both clinically normal cows and those diagnosed with endometritis, ensuring a comprehensive evaluation of the diagnostic methods across different stages of uterine health. The following laboratory tests were performed to diagnose and evaluate the presence and severity of endometritis in the cows: Nagorny-Kalinovsky test, Whiteside test, Katerinov test, Gavrish silver nitrate test, peroxide test, and clinical tests (rectal and vaginal examination). These tests were specifically chosen to identify inflammatory processes in the uterus, particularly focusing on detecting endometritis. Results: From day 21 to 30 PP, rectal and vaginal examinations were 32% and 28% more effective than the Nagorny-Kalinovsky test and the Whiteside test. From day 61 postpartum, the Whiteside test was 37.5% more effective than the Nagorny-Kalinovsky test. Comparatively, among laboratory diagnostic methods from days 10 to 110 PP, the peroxide test showed the greatest effectiveness in identifying 80.9% of sick animals. In sick animals from day 10 to 20 PP, during the interaction of the cervicovaginal mucus with 10%, 20%, and 30% hydrogen peroxide (H2 O2 ), an 8.1 ± 1.9–8.8 ± 1.6 cm foam column was formed within 4–5 min. Conclusion: The experiment showed that a 10% H2 O2 solution yielded better results. Using H2 O2 as a diagnostic agent for endometritis in cows has several advantages, including ease of use, it does not require special laboratory conditions and provides a visual reading of the reaction within 4–5 min. A limitation of this study is the focus on H2 O2 without exploring other potential reagents that may enhance diagnostic accuracy. Future research could explore the long-term stability of cervicovaginal mucus samples and investigate the integration of additional substances that may expedite the detection of subclinical endometritis and improve the clarity of diagnostic results. [ABSTRACT FROM AUTHOR]

Chronic endometritis (CE) is a frequent pathological condition that is defined as localized inflammation in the endometrium. Some adverse fertility consequences such as recurrent miscarriage and failure of implantation are associated with chronic endometritis. On the one hand, inflammation plays an important role in the pathogenesis of endometritis, and on the other hand, the role of viral infections in inducing inflammation can make this review strongly attractive and practical. We set out to provide an overview of viral infections as a potential etiology of CE pathophysiology through the alteration of an endometrial microenvironment and its association with infertility. To the best of our knowledge, this is the first review to demonstrate the role of viral infection in chronic endometritis, and whether or not infection ultimately plays a role.. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the correlation between hysteroscopic findings of chronic endometritis and CD138 immunohistochemistry positive in endometritis and to analyze the pregnancy outcomes and associated risk factors following embryo transfer in women diagnosed with chronic endometritis via hysteroscopy. Methods: A retrospective observational study carried out at the Reproductive Medicine Center of Tangdu Hospital of Air Force Medical University, from January 2021 to December 2021, was performed by obtaining data from 194 medical records of women who underwent hysteroscopies for infertility and were diagnosed with chronic endometritis based on Delphi criteria. Spearman correlation analysis was used to evaluate the correlation between hysteroscopic findings and endometrial CD138 immunohistochemistry. The study also observed the differences in relevant indexes between the CD138-positive and CD138-negative groups after embryo transfer and analyzed factors influencing implantation failure using logistic regression analysis. Results: The correlation analysis between hysteroscopic findings and CD138 immunohistochemistry showed that micropolyps were correlated with CD138 immunohistochemistry positivity. The correlation coefficient was 0.32 (P < 0.01). After embryo transfer, the clinical pregnancy rate of the CD138-positive group was lower compared to that of the CD138-negative group [64.79% (46/71) vs. 81.30% (100/123), P < 0.05]. The results of the multivariate logistic regression analysis revealed that age (P = 0.43) and CD138 immunohistochemistry positivity (P = 0.008) were the independent risk factors for predicting whether or not embryo implantation was successful. Conclusion: Hysteroscopic findings do not correlate strongly with endometrial CD138 immunohistochemistry, and chronic endometritis cannot be diagnosed by hysteroscopy alone. CD138 immunohistochemistry positivity is an independent factor contributing to the decrease in clinical pregnancy rate following embryo transfer. [ABSTRACT FROM AUTHOR]

The endocannabinoid system (ECS) plays a crucial role in reproductive health, but its function in postpartum dairy cows remains poorly understood. This study investigated the expression patterns of ECS-related genes in the endometrium of postpartum dairy cows and their associations with endometrial health and the presence of fatty liver. Endometrial biopsies were collected from 22 Holstein Friesian cows at 4 and 7 weeks postpartum. Gene expression was analyzed using RT-qPCR, focusing on key ECS components including CNR2, MGLL, FAAH1, NAAA, NAPEPLD, PADI4 and PTGDS. The results reveal dynamic changes in ECS gene expression associated with endometritis and fatty liver. MGLL expression was significantly upregulated in cows with endometritis at 7 weeks postpartum, while NAAA expression was consistently downregulated in cows with fatty liver. CNR2 showed a time-dependent pattern in endometritis, and PTGDS expression was elevated in clinical endometritis at 4 weeks postpartum. The presence of fatty liver was associated with altered expression patterns of several ECS genes, suggesting a link between metabolic stress and endometrial ECS function. These findings indicate a potential role for the ECS in postpartum uterine health and recovery, offering new insights into the molecular mechanisms underlying reproductive disorders in dairy cows and paving the way for novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

BACKGROUND The establishment and maintenance of pregnancy depend on endometrial competence. Asherman syndrome (AS) and intrauterine adhesions (IUA), or endometrial atrophy (EA) and thin endometrium (TE), can either originate autonomously or arise as a result from conditions (i.e. endometritis or congenital hypoplasia), or medical interventions (e.g. surgeries, hormonal therapies, uterine curettage or radiotherapy). Affected patients may present an altered or inadequate endometrial lining that hinders embryo implantation and increases the risk of poor pregnancy outcomes and miscarriage. In humans, AS/IUA and EA/TE are mainly treated with surgeries or pharmacotherapy, however the reported efficacy of these therapeutic approaches remains unclear. Thus, novel regenerative techniques utilizing stem cells, growth factors, or tissue engineering have emerged to improve reproductive outcomes. OBJECTIVE AND RATIONALE This review comprehensively summarizes the methodologies and outcomes of emerging biotechnologies (cellular, acellular, and bioengineering approaches) to treat human endometrial pathologies. Regenerative therapies derived from human tissues or blood which were studied in preclinical models (in vitro and in vivo) and clinical trials are discussed. SEARCH METHODS A systematic search of full-text articles available in PubMed and Embase was conducted to identify original peer-reviewed studies published in English between January 2000 and September 2023. The search terms included: human, uterus, endometrium, Asherman syndrome, intrauterine adhesions, endometrial atrophy, thin endometrium, endometritis, congenital hypoplasia, curettage, radiotherapy, regenerative therapy, bioengineering, stem cells, vesicles, platelet-rich plasma, biomaterials, microfluidic, bioprinting, organoids, hydrogel, scaffold, sheet, miRNA, sildenafil, nitroglycerine, aspirin, growth hormone, progesterone, and estrogen. Preclinical and clinical studies on cellular, acellular, and bioengineering strategies to repair or regenerate the human endometrium were included. Additional studies were identified through manual searches. OUTCOMES From a total of 4366 records identified, 164 studies (3.8%) were included for systematic review. Due to heterogeneity in the study design and measured outcome parameters in both preclinical and clinical studies, the findings were evaluated qualitatively and quantitatively without meta-analysis. Groups using stem cell-based treatments for endometrial pathologies commonly employed mesenchymal stem cells (MSCs) derived from the human bone marrow or umbilical cord. Alternatively, acellular therapies based on platelet-rich plasma (PRP) or extracellular vesicles are gaining popularity. These are accompanied by the emergence of bioengineering strategies based on extracellular matrix (ECM)-derived hydrogels or synthetic biosimilars that sustain local delivery of cells and growth factors, reporting promising results. Combined therapies that target multiple aspects of tissue repair and regeneration remain in preclinical testing but have shown translational value. This review highlights the myriad of therapeutic material sources, administration methods, and carriers that have been tested. WIDER IMPLICATIONS Therapies that promote endometrial proliferation, vascular development, and tissue repair may help restore endometrial function and, ultimately, fertility. Based on the existing evidence, cost, accessibility, and availability of the therapies, we propose the development of triple-hit regenerative strategies, potentially combining high-yield MSCs (e.g. from bone marrow or umbilical cord) with acellular treatments (PRP), possibly integrated in ECM hydrogels. Advances in biotechnologies together with insights from preclinical models will pave the way for developing personalized treatment regimens for patients with infertility-causing endometrial disorders such as AS/IUA, EA/TE, and endometritis. REGISTRATION NUMBER https://osf.io/th8yf/ [ABSTRACT FROM AUTHOR]

The results of an experiment assessing the applicability of solutions of 6-oxo-2-phenylimidazo[1,2-b]pyrido[4,3-e][1,2,4]triazine-7(6H)-yl)acetic acid on plates and cellulose substrates for detecting excessive levels of volatile organic compounds associated with endometritis inflammation relative to biologically normal levels are considered. The fluorescent properties of the dye are studied using gynecological mucus from cows collected in various periods (pre- and post-partum) and nasal mucus from newborn calves. The test system responses were compared with clinically established diagnoses and the results of a microbiological study. An evaluation of the test systems revealed a false positive rate of no more than 11% and a false negative rate of 2%. Other characteristics, such as specificity, accuracy, and precision of the test systems based on 6-oxo-2-phenylimidazo[1,2-b]pyrido[4,3-e][1,2,4]triazine-7(6H)-yl)acetic acid were also assessed. The potential application of this fluorophore to the rapid on-site diagnosis of endometritis inflammation in cows is considered promising based on these findings. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Our objective was to investigate the effects of intravenous (IV) or intrauterine (IU) lipopolysaccharide (LPS) challenge at 5 or 40 d postpartum (DPP) on clinical signs, systemic and uterine inflammation, dry matter intake (DMI), and milk yield (MY). Holstein cows at 5 DPP (n = 23) or at 40 DPP (n = 24) were blocked by parity and randomly assigned to 1 of 3 treatments: (1) IV-LPS (0.0625 μg/kg BW [5 DPP] or 0.1 μg/kg BW [40 DPP] over 1h), (2) IU-LPS (100 μg [5 DPP] or 300 μg [40 DPP] in 20 mL of saline), or (3) 20 mL of saline IU (IU-SAL; same for 5 and 40 DPP). The proportion of polymorphonuclear (PMN) cells was measured by endometrial cytology at d −1, 1, 4, and 7 relative to treatment. Blood haptoglobin (Hp), serum amyloid A (SAA), and LPS-binding protein (LBP), DMI, and MY were measured from d −1 through d 7. Data were analyzed separately for each DPP group in multivariable linear regression models accounting for repeated measures. Both DPP groups showed increases in rectal temperature and heart and respiratory rates, and decrease in rumination rate following IV-LPS, but not following IU-LPS. At 5 DPP, endometrial PMN proportion was similar in IU-LPS and IU-SAL. Serum Hp was unaffected by LPS challenge, SAA was greater in IV-LPS from 12 h to 24 h after challenge, and LBP was greater in IV-LPS from 8 h to 24 h. At 40 DPP, PMN was greater in IU-LPS (37 ± 4%) than in IU-SAL (15 ± 4%) 1 d after LPS challenge. Serum Hp was greater from 24 h to 72 h after challenge in IV-LPS than in the other groups, SAA was greater in IV-LPS from 6 h to 48 h, and LBP was greater in IV-LPS from 8 h to 24 h. At both 5 and 40 DPP, treatment did not affect DMI, but MY was lesser in IV-LPS cows at 12 h and 24 h than in IU-SAL or IU-LPS. The IV-LPS challenge resulted in more pronounced changes in clinical signs and acute phase protein (APP) concentrations than IU-LPS or IU-SAL at 40 DPP, but more subtle or inconsistent changes at 5 DPP. These may be due to the different doses of LPS used at 5 and 40 DPP or possibly due to the high variation in baseline clinical signs and APP observed in all groups at 5 DPP. The IU-LPS increased uterine PMN 1 d after challenge at 40 DPP but not at 5 DPP. At each time, IU-LPS did not produce changes in clinical signs or markers of systemic inflammation. [ABSTRACT FROM AUTHOR]

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Abstract Research exploring the link between immune cell profiles and the development of endometritis remains scant. This gap necessitates further study to decode the complex interrelations influencing this condition. In this analysis, we leveraged two-sample Mendelian randomization to examine the causal ties between the phenotypes of immune cells and the incidence of endometritis. Our evaluation hinged on data from 3757 participants hailing from Sardinia, focusing on a diverse array of 731 immune phenotypes, and cross-referenced with endometritis data sourced from the UK Biobank. To ensure rigor, we performed sensitivity analyses, utilized MR-Egger and MR-Presso to check for pleiotropy, and applied Cochran’s Q test for assessing the heterogeneity of our findings. Our investigation identified numerous immune characteristics associated with endometritis. For certain immune traits, a lower risk of endometritis was observed, including: Absolute Counts of CD39 + CD4 + T cells, CD25 + CD39 + CD4 regulatory T cells, and CD25 + + CD8 + T cells; Absolute Counts of Switched Memory B cells; CD19 expression on IgD + CD38dim and Switched Memory B cells; CD20 expression on IgD + CD38− Unswitched Memory B cells; percentage of Switched Memory B cells among lymphocytes; CD16-CD56 expression on HLA DR + Natural Killer cells; percentage of CD11c + CD62L− monocytes; CD86 expression on monocytes; CCR2 expression on CD14 + CD16 + monocytes; and CD14 expression on Monocytic Myeloid-Derived Suppressor Cells, with Odds Ratios (ORs) between 0.413 and 0.703. On the contrary, increased risks of endometritis were linked with: the percentage of Effector Memory CD4 + T cells within the CD4 + T cell population; percentages of HLA DR + T cells and HLA DR + CD8 + T cells among T cells; CD4 expression on CD28 + CD4 + T cells; CD20 expression on CD20- CD38- B cells; percentage of IgD + CD24 + B cells within the B cell population; CD62L expression on CD62L + myeloid Dendritic Cells; and Absolute Counts of Plasmacytoid Dendritic Cells, with ORs from 1.473 to 2.677, indicating these traits potentially elevate the risk of developing endometritis. Our research delineates distinct causal links between specific immune cell phenotypes and endometritis, offering new perspectives that could contribute to the pinpointing of new therapeutic avenues for this condition.

Background and Aim: Postpartum uterine disease, such as endometritis, is widespread in highly productive dairy cows, leading to fertility problems and economic losses. Despite existing diagnostic methods, early and effective detection of uterine infections remains problematic due to the subclinical nature of some conditions. This study aimed to develop and evaluate a rapid diagnostic test for endometritis in cows on different days postpartum (PP). Materials and Methods: The study was carried out on dairy Holstein–Friesian cows (n = 121) kept on farms in northern Kazakhstan. The study included both clinically normal cows and those diagnosed with endometritis, ensuring a comprehensive evaluation of the diagnostic methods across different stages of uterine health. The following laboratory tests were performed to diagnose and evaluate the presence and severity of endometritis in the cows: Nagorny-Kalinovsky test, Whiteside test, Katerinov test, Gavrish silver nitrate test, peroxide test, and clinical tests (rectal and vaginal examination). These tests were specifically chosen to identify inflammatory processes in the uterus, particularly focusing on detecting endometritis. Results: From day 21 to 30 PP, rectal and vaginal examinations were 32% and 28% more effective than the Nagorny-Kalinovsky test and the Whiteside test. From day 61 postpartum, the Whiteside test was 37.5% more effective than the Nagorny-Kalinovsky test. Comparatively, among laboratory diagnostic methods from days 10 to 110 PP, the peroxide test showed the greatest effectiveness in identifying 80.9% of sick animals. In sick animals from day 10 to 20 PP, during the interaction of the cervicovaginal mucus with 10%, 20%, and 30% hydrogen peroxide (H2O2), an 8.1 ± 1.9–8.8 ± 1.6 cm foam column was formed within 4–5 min. Conclusion: The experiment showed that a 10% H2O2 solution yielded better results. Using H2O2 as a diagnostic agent for endometritis in cows has several advantages, including ease of use, it does not require special laboratory conditions and provides a visual reading of the reaction within 4–5 min. A limitation of this study is the focus on H2O2 without exploring other potential reagents that may enhance diagnostic accuracy. Future research could explore the long-term stability of cervicovaginal mucus samples and investigate the integration of additional substances that may expedite the detection of subclinical endometritis and improve the clarity of diagnostic results.

ABSTRACT: Our objective was to investigate the effects of intravenous (IV) or intrauterine (IU) lipopolysaccharide (LPS) challenge at 5 or 40 d postpartum (DPP) on clinical signs, systemic and uterine inflammation, dry matter intake (DMI), and milk yield (MY). Holstein cows at 5 DPP (n = 23) or at 40 DPP (n = 24) were blocked by parity and randomly assigned to 1 of 3 treatments: (1) IV-LPS (0.0625 μg/kg BW [5 DPP] or 0.1 μg/kg BW [40 DPP] over 1h), (2) IU-LPS (100 μg [5 DPP] or 300 μg [40 DPP] in 20 mL of saline), or (3) 20 mL of saline IU (IU-SAL; same for 5 and 40 DPP). The proportion of polymorphonuclear (PMN) cells was measured by endometrial cytology at d −1, 1, 4, and 7 relative to treatment. Blood haptoglobin (Hp), serum amyloid A (SAA), and LPS-binding protein (LBP), DMI, and MY were measured from d −1 through d 7. Data were analyzed separately for each DPP group in multivariable linear regression models accounting for repeated measures. Both DPP groups showed increases in rectal temperature and heart and respiratory rates, and decrease in rumination rate following IV-LPS, but not following IU-LPS. At 5 DPP, endometrial PMN proportion was similar in IU-LPS and IU-SAL. Serum Hp was unaffected by LPS challenge, SAA was greater in IV-LPS from 12 h to 24 h after challenge, and LBP was greater in IV-LPS from 8 h to 24 h. At 40 DPP, PMN was greater in IU-LPS (37 ± 4%) than in IU-SAL (15 ± 4%) 1 d after LPS challenge. Serum Hp was greater from 24 h to 72 h after challenge in IV-LPS than in the other groups, SAA was greater in IV-LPS from 6 h to 48 h, and LBP was greater in IV-LPS from 8 h to 24 h. At both 5 and 40 DPP, treatment did not affect DMI, but MY was lesser in IV-LPS cows at 12 h and 24 h than in IU-SAL or IU-LPS. The IV-LPS challenge resulted in more pronounced changes in clinical signs and acute phase protein (APP) concentrations than IU-LPS or IU-SAL at 40 DPP, but more subtle or inconsistent changes at 5 DPP. These may be due to the different doses of LPS used at 5 and 40 DPP or possibly due to the high variation in baseline clinical signs and APP observed in all groups at 5 DPP. The IU-LPS increased uterine PMN 1 d after challenge at 40 DPP but not at 5 DPP. At each time, IU-LPS did not produce changes in clinical signs or markers of systemic inflammation.

Endometritis is an inflammatory and histopathologic disease in uterine tissues that interferes with the proper decidualization and implantation of the embryo. In this study, rosmarinic acid (RA) is used as an anti-inflammatory agent that encapsulates in exosomes and is used to attenuate lipopolysaccharide (LPS)-induced endometritis and improve implantation. For this purpose, exosomes were loaded with RA and then administrated into the animal groups, including RA, exosome, RA plus exosome (RA + Exo), and RA-loaded exosomes (RALExo) groups. The concentrations of RA or exosomes used in this study were 10 mg/kg, and the compounds were injected into the uterine horn 24 h following the induction of endometritis. Upon the presence of inflammation detected by the histopathological method, the most proper groups were mated with male mice. The effect of the treatment group on the implantation rate, progesterone levels, and gene expressions were assessed by Chicago Blue staining, enzyme-linked immunosorbent assay (ELISA), and Quantitative PCR (qPCR), respectively. Results showed RALExo10 and RA10 + Exo10 groups improved pathological alterations, enhanced progesterone levels, increased implantation rate, as well as heightened expression levels of Leukemia inhibitory factor (LIF) and Mucin-16 (MUC-16) genes. Besides, the expression levels of inflammatory cytokines, including Transforming growth factor-β (TGF-β), Interlukine-10 (IL-10), Interlukine-15 (IL-15), and Interlukine-18 (IL-18), were regulated. Our findings indicated that the expression of LIF, Muc-16 genes as well as IL-18, were significantly correlated with serum progesterone concentrations and the implantation rate in the treatment groups. The RALExo10 and RA10 + Exo10 groups showed ameliorated implantation rates in experimental groups. [ABSTRACT FROM AUTHOR]

Abstract Background The role of bacterial contamination in the development and progression of endometriosis lesions is currently a hot topic for gynecologists. In this study, we decided to compare the endometrial cultures of women affected by endometriosis with those of non-endometriotic women, focusing on specific microbial pathogens. Material and method In this cross-sectional case-control study, 30 women with endometriosis in stages 4 of the disease whose endometriosis was confirmed based on clinical, ultrasound, and histopathological findings, and 30 women without endometriosis who were candidates for surgery due to benign uterine diseases with regular menstrual cycle, underwent endometrial biopsy with Novak Kort in sterile conditions before starting their operation, and the results of their endometrial culture were analyzed and compared. Results Results of the study indicate that there were no significant differences in terms of age, BMI, smoking, education level, place of residency, use of the intrauterine device, or vaginal douche, and age of menarche between the case and control groups. The only demographic difference observed was in parity, where the control group had a significantly higher parity than the case group (P = 0.001). Out of the 60 cultures, only 15 samples were positive in the endometriosis group, and E. coli was the most prevalent species, with 10 (33.3%) samples testing positive for it. Klebsiella spp. and Enterobacteria spp. were also detected in 3 (10.0%) and 2 (6.7%) samples, respectively. The comparison between the two groups showed that only E. coli had a significant association with the presence of endometriosis (P = 0.001). There was no significant relationship between the location of endometriosis in the pelvic cavity and culture results. It was observed that parity among the E. coli negative group was significantly higher compared to the E. coli positive group (P

Introduction: Postpartum endometritis is a prevalent reproductive disorder in bovines, leading to a prolonged open period, infertility, and other complications. While Lactobacillus strains can mitigate these conditions by reducing uterine inflammation, their effectiveness is limited due to a lack of direct anti microbial action and extended treatment duration. This study aimed to construct a recombinant Lactobacillus johnsonii strain expressing bovine Granulocytemacrophage colony-stimulating factor (GM-CSF) to evaluate its potential in reducing postpartum uterine inflammation. Methods: The recombinant Lactobacillus johnsonii strain was engineered to express bovine GM-CSF and administered to pregnant mice via vaginal perfusion. Postpartum endometritis was induced using E. coli infection, and the protective effects of the engineered strain were assessed. Inflammatory markers (IL-6, IL-1β, TNF-α), myeloperoxidase (MPO) activity, and nitric oxide (NO) concentration were measured. Histological examination was performed to evaluate uterine morphology and pathological damage. Results: The recombinant L. johnsonii strain expressing GM-CSF significantly reduced inflammation levels induced by E. coli infection in the uterus. This reduction was evidenced by decreased expression of IL-6, IL-1β, TNF-α, as well as reduced MPO activity and NO concentration. Histological examination revealed improved uterine morphology and reduced pathological damage in mice treated with the recombinant GM-CSF strain. Crucially, the recombinant strain also exerts beneficial effects on bovine endometritis by reducing levels of inflammatory cytokines, suggesting a beneficial effect on clinical bovine endometritis. Conclusion: The recombinant Lactobacillus johnsonii expressing GM-CSF demonstrated protective effects against postpartum endometritis in bovines by reducing inflammatory cytokines. The findings indicate the potential clinical application of this engineered strain in preventing postpartum uterine inflammation, offering a novel and effective protective option for related disorders and improving bovine reproductive efficiency. [ABSTRACT FROM AUTHOR]

Objectives: This prospective study evaluated whether endometriosis is associated with chronic endometritis (CE) and affects the uterine endometrium microbiome (UEM) in women with repeated implantation failure (RIF). Methods: Forty-three women with RIF were divided into 12 with endometriosis (EM) and 31 without endometriosis (non-EM). The UEM was examined by 16S ribosomal RNA (rRNA) sequencing, and CE was determined by CD 138 staining (plasma cells > 5.15/10 mm2) simultaneously. Results: The EM group had a higher bacterial number (EM vs. non-EM; median [range], 6.5 vs. 3 [3–11, 1–16], p = 0.009), while the frequency of Lactobacillus species did not change. The rates of presence of Dialister (41.7% [5/12] vs. 3.3% [1/31], p = 0.004) and Streptococcus species (58.3% [7/12] vs. 16.1% [5/31], p = 0.017) were higher in the EM group. The prevalence of CE did not differ between the two groups. Multivariable logistic regression analysis revealed that the presence of Dialister species (odds ratio, 10.97, 95% confidence interval, 1.17–249.37, p = 0.036) was associated with endometriosis. In the EM group, five women with Dialister species had a higher number of bacterial species (10 vs. 5 [6–11, 3–7], p = 0.021) and higher Shannon diversity index (0.50 vs. 0.20 [0.19–1.39, 0.03–0.46], p = 0.026) than seven without Dialister species. Conclusions: Dialister and Streptococcus species, and the increased number of bacterial species in UEM may be related to the pathogenesis of RIF complicated by endometriosis. [ABSTRACT FROM AUTHOR]

Simple Summary: The aims of this study are to analyze prevalence rates, influence, and genetic parameters (heritability, genetic, and phenotypic correlations) of mastitis (MAS), endometritis (MET), and ketosis (KET) in Chinese Holstein Cattle. Data from 37,836 dairy cows in Central China were analyzed using the logistic regression method, a mixed linear model, and an animal model (BLUP). The prevalence rates of MAS, MET, and KET were 20.04%, 10.68%, and 7.33%, respectively. MAS and MET had a negative effect on production traits. High-milk yield cows had high KET prevalence rates. MAS, MET, and KET all had negative influences on reproduction traits. The heritabilities of predispositions to MAS, MET, and KET were 0.09, 0.01, and 0.02, respectively. Mastitis (MAS), endometritis (MET), and ketosis (KET) are prevalent diseases in dairy cows that result in substantial economic losses for the dairy farming industry. This study gathered 26,014 records of the health and sickness of dairy cows and 99,102 data of reproduction from 13 Holstein dairy farms in Central China; the milk protein and milk fat content from 56,640 milk samples, as well as the pedigree data of 37,836 dairy cows were obtained. The logistic regression method was used to analyze the variations in the prevalence rates of MAS, MET, and KET among various parities; the mixed linear model was used to examine the effects of the three diseases on milk production, milk quality, and reproductive traits. DMU software (version 5.2) utilized the DMUAI module in conjunction with the single-trait and two-trait animal model, as well as best linear unbiased prediction (BLUP), to estimate the genetic parameters for the three diseases, milk production, milk quality, and reproductive traits in dairy cows. The primary findings of the investigation comprised the following: (1) The prevalence rates of MAS, MET, and KET in dairy farms were 20.04%, 10.68%, and 7.33%, respectively. (2) MAS and MET had a substantial impact (p < 0.01) on milk production, resulting in significant decreases of 112 kg and 372 kg in 305-d Milk Yield (305-d MY), 4 kg and 12 kg in 305-d Protein Yield (305-d PY), and 6 kg and 16 kg in 305-d Fat Yield (305-d FY). As a result of their excessive 305-d MY, some cows were diagnosed with KET due to glucose metabolism disorder. The 305-d MY of cows with KET was significantly higher than that of healthy cows (205 kg, p < 0.01). (3) All three diseases resulted in an increase in the Interval from Calving to First Service (CTFS, 0.60–1.50 d), Interval from First Service to Conception (FSTC, 0.20–16.20 d), Calving Interval (CI, 4.00–7.00 d), and Number of Services (NUMS, 0.07–0.35). (4) The heritabilities of cows with MAS, MET, and KET were found to be low, with values of 0.09, 0.01, and 0.02, respectively. The genetic correlation between these traits ranged from 0.14 to 0.44. This study offers valuable insights on the prevention and control of the three diseases, as well as feeding management and genetic breeding. [ABSTRACT FROM AUTHOR]

There is limited research on risk factors for chronic endometritis regarding reproductive history and clinical symptoms. Thus, this nested case–control study identified risk factors for chronic endometritis in women who have undergone hysteroscopy. Endometrial tissue sections were obtained from 502 women with intrauterine disorders who underwent hysteroscopy. Chronic endometritis was diagnosed via CD138 immunostaining. The women were divided into two groups: 271 women without chronic endometritis and 231 women with chronic endometritis. The prevalence of chronic endometritis was 46%. Univariate logistic regression revealed that prolonged menstruation and intermenstrual bleeding were associated with chronic endometritis, and subsequent multivariate logistic regression analyses showed that these were further independently associated. With univariable logistic regression, the gravidity and abortion history were correlated with chronic endometritis; however, no significant correlation was found with the adjusted odds ratio (OR) of 0.74 (95% confidence interval [CI] 0.46–1.19) or 0.76 (95% CI 0.58–1.11), respectively. No significant correlation was found between caesarean section history and the rates of chronic endometritis. No significant difference was found in all other variables between the three groups with > 5, ≤ 5 plasma cells and in a unknown group. Prolonged menstruation and intermenstrual bleeding were risk factors associated with chronic endometritis. Chronic endometritis should be considered and CD138 immunohistochemical examination should be recommended in women with these symptoms. [ABSTRACT FROM AUTHOR]

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Simple Summary: Endometritis is defined as a localized inflammatory condition of the endometrium that results in significant financial losses. This investigation used forty buffalo cows with clinical endometritis that were infected and forty seemingly healthy buffalo cows who served as the control group made up the two groups of buffalo cows. The expression levels and the serum characteristics of immune and antioxidant biomarkers linked to clinical endometritis risk varied between the investigated two categories of buffalo cows. The alteration in the profile of explored markers suggests a potential source for uterine health indicators in buffaloes. Determining the gene expression and serum profile of the indicators linked to clinical endometritis susceptibility in Egyptian buffalo cows was the aim of this investigation. The buffalo cows that were enrolled were divided into two groups: forty infected buffalo cows with clinical endometritis and forty seemingly healthy buffalo cows that served as the control group. For the purposes of gene expression and biochemical analysis, ten milliliters of blood was obtained via jugular venipuncture from each buffalo cow. TLR4, IL-8, IL-17, NFKB, SLCA11A1, NCF4, Keap1, HMOX1, OXSR1, ST1P1, and SERP1 were manifestly expressed at much higher levels in the buffaloes with endometritis. On the other hand, the genes that encode SOD, CAT, NDUFS6, Nrf2, and PRDX2 were down-regulated. There was a significant (p < 0.05) elevation of the serum levels of non-esterified fatty acids (NEFAs), beta hydroxy butyric acid (BHBA), triglycerides (TGs), globulin, creatinine, and cortisol, along with a reduction in the serum levels of glucose, cholesterol, total protein albumin, urea, estrogen (E2), progesterone (P4), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroxine (T4), prostaglandin F2 α (PGF2α), calcium, iron, and selenium, in the endometritis group in comparison with the control. However, no significant change was observed in the values of phosphorus, magnesium, copper, or zinc in either group. Within the selective breeding of naturally resistant animals, the variation in the genes under study and the changes in the serum profiles of the indicators under investigation may serve as a reference guide for reducing endometritis in Egyptian buffalo cows. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the impact of antibiotic treatment for chronic endometritis (CE) on the pregnancy outcome of frozen-thawed embryo transfer (FET) cycles and the relevant clinical risk factors associated with CE. Methods: A retrospective cohort analysis was conducted on 1352 patients who underwent hysteroscopy and diagnostic curettage at Nanjing Maternal and Child Health Hospital from July 2020 to December 2021. All patients underwent CD138 immunohistochemical (IHC) testing to diagnose CE, and a subset of them underwent FET after hysteroscopy. Patient histories were collected, and reproductive prognosis was followed up. Results: Out of 1088 patients, 443 (40.7%) were diagnosed with CE. Univariate and multivariate binary logistic regression analyses revealed that parity ≥ 2, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, hydrosalpinx, endometrial polyps, a history of ≥ 2 uterine operations, and RIF were significantly associated with an elevated risk of CE (P < 0.05). Analysis of the effect of CE on pregnancy outcomes in FET cycles after antibiotic treatment indicated that treated CE patients exhibited a significantly lower miscarriage rate (8.7%) and early miscarriage rate (2.9%) than untreated non-CE patients (20.2%, 16.8%). Moreover, the singleton live birth rate (45.5%) was significantly higher in treated CE patients than in untreated non-CE patients (32.7%). Survival analysis revealed a statistically significant difference in the first clinical pregnancy time between treated CE and untreated non-CE patients after hysteroscopy (P = 0.0019). Stratified analysis based on the presence of recurrent implantation failure (RIF) demonstrated that in the RIF group, treated CE patients were more likely to achieve clinical pregnancy than untreated non-CE patients (P = 0.0021). Among hysteroscopy-positive patients, no significant difference was noted in pregnancy outcomes between the treatment and control groups (P > 0.05). Conclusion: Infertile patients with a history of parity ≥ 2, hydrosalpinx, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, endometrial polyps, a history of ≥ 2 uterine operations, and RIF are at an increased risk of CE; these patients should be recommended to undergo hysteroscopy combined with CD138 examination before embryo transfer. Antibiotic treatment can improve the reproductive outcomes of FET in patients with CE, especially those with RIF. [ABSTRACT FROM AUTHOR]

Objective: The aim was to develop a predictive tool for anticipating postpartum endometritis occurrences and to devise strategies for prevention and control. Methods: Employing a retrospective approach, the baseline data of 200 women diagnosed with postpartum endometritis in a tertiary maternity hospital in Zhejiang Province, spanning from February 2020 to September 2022, was examined. Simultaneously, the baseline data of 1,000 women without endometritis during the same period were explored with a 1:5 ratio. Subsequently, 1,200 women were randomly allocated into a training group dataset and a test group dataset, adhering to a 7:3 split. The selection of risk factors for postpartum endometritis involved employing random forests, lasso regression, and traditional univariate and multifactor logistic regression on the training group dataset. A nomogram was then constructed based on these factors. The model's performance was assessed using the area under the curve (AUC), calculated through plotting the receiver operating characteristic (ROC) curve. Additionally, the Brier score was employed to evaluate the model with a calibration curve. To gauge the utility of the nomogram, a clinical impact curve (CIC) analysis was conducted. This comprehensive approach not only involved identifying risk factors but also included a visual representation (nomogram) and thorough evaluation metrics, ensuring a robust tool for predicting, preventing, and controlling postpartum endometritis. Results: In the multivariate analysis, six factors were identified as being associated with the occurrence of maternal endometritis in the postpartum period. These factors include the number of negative finger tests (OR: 1.159; 95%CI: 1.091–1.233; P < 0.05), postpartum hemorrhage (1.003; 1.002–1.005; P < 0.05), pre-eclampsia (9.769; 4.64–21.155; P < 0.05), maternity methods (2.083; 1.187–3.7; P < 0.001), prenatal reproductive tract culture (2.219; 1.411–3.47; P < 0.05), and uterine exploration (0.441; 0.233–0.803; P < 0.001).A nomogram was then constructed based on these factors, and its predictive performance was assessed using the area under the curve (AUC). The results in both the training group data (AUC: 0.803) and the test group data (AUC: 0.788) demonstrated a good predictive value. The clinical impact curve (CIC) further highlighted the clinical utility of the nomogram. Conclusion: The development of an individualized nomogram for postpartum endometritis infection holds promise for doctors in screening high-risk women, enabling early intervention and ultimately reducing the rate of postpartum endometritis infection. This comprehensive approach, integrating key risk factors and predictive tools, enhances the potential for timely and targeted medical intervention. [ABSTRACT FROM AUTHOR]

The experiment is designed to explore the impact of Yimu Shenghuasan on the serum hormone levels and the expression levels of factors related to the TLR4/NF-κB signaling pathway in a mouse model of endometritis. A total of 40 female mice, with similar age, body size, and weight, were randomly divided into four groups with 10 replicates per group and one mouse per replicate. Mice in the control group were instillated with 20 μL normal saline, the model group was instillated with 25 μL lipopolysaccharide (LPS, 1 g/L), the drug group was instillated with 2.0 g/kg Yimu Shenghuasan, and the treatment group was instillated with 25 μL LPS + 2.0 g/kg Yimu Shenghuasan, continuously gavage for three days, twice a day. The contentrations of estradiol (E2), progesterone (Pg), luteinizing hormone (LH), and folliclestimulating hormone (FSH) in the serum was detected by radioimmunoassay, the contentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) in the serum was detected by ELISA method, and the expression of factors related to the TLR4/NF-κB signaling pathway, including Toll-like receptor 4 (TLR4), myeloid differentiation factor (MyD88), nuclear factor-κB p65 (NF-κB p65), IL-1β, IL-6, IL-8, TNF-α mRNA was detected by RT-PCR method. The results showed that compared with the control group, the serum E2, LH, and FSH contentrations in the model group was significantly reduced, while Pg content increased, the secretion and mRNA gene expression of IL-1β, IL-6, IL-8, and TNF-α were significantly increased, and the expression of TLR4, MyD88, NF-κB p65 mRNA was significantly upregulated. Compared with the model group, the serum E2, LH, and FSH content in the treatment group was significantly increased, Pg content reduced, the secretion and mRNA gene expression of IL-6, IL-8, IL-1β, and TNF-α were significantly reduced, and the expression of TLR4, MyD88, NF-κB p65 mRNA was significantly downregulated. The study indicates that Yimu Shenghuasan, by regulating the content of hormones and inhibiting the changes in the levels of factors related to the TLR4/NF-κB signaling pathway, has a relieving effect on LPS-induced mouse endometriosis. [ABSTRACT FROM AUTHOR]

Summary Hysteroscopy is a complementary tool to the traditional transrectal palpation and ultrasonography commonly performed by equine practitioners. Once mastered, it is a quick and useful diagnostic tool for the general and targeted evaluation of the endometrium and provides real time information about potential causes of subfertility. Samples of intrauterine fluid and the endometrium can be taken via transendoscopic catheters or infusion pipettes or via the use of traditional endometrial biopsy forceps. In addition to being a useful diagnostic tool, treatments can often be performed at the same time the pathologies are identified, providing mare owners with information and resolution of problems. With the development of additional technologies, hysteroscopy allows for optical biopsies to be performed, which will likely increase in use as the software moves from the research laboratories to clinical practice. Hysteroscopy is an easily learned, useful clinical skill for the identification of abnormalities in the mares' reproductive tract. [ABSTRACT FROM AUTHOR]

Background: To explore the incidence of chronic endometritis (CE) in patients with infertility and different forms of adenomyosis and analyze potential high-risk factors for infection. Methods: This retrospective cohort study included 154 patients with infertility in the Liuzhou Maternity and Child Healthcare Hospital. Among them, 77 patients with adenomyosis were divided into four subgroups based on magnetic resonance imaging (MRI): internal, exterior, intramural, and full-thickness. Meanwhile, 77 patients did not have adenomyosis. Hysteroscopy and endometrial biopsy were performed in the proliferative phase. The main outcome measures were the morphology of the endometrium, syndecan-1 (CD138) immunohistochemical staining, clinical characteristics, and prevalence of CE in the adenomyosis subgroups. Results: In comparison to the non-adenomyosis group, the adenomyosis group had significantly higher body mass index (BMI) and CA125 levels. The menstrual cycle in the adenomyosis group was significantly shorter, and menarche was significantly earlier. In comparison to the non-adenomyosis group, the adenomyosis group had a significantly higher diagnostic rate of CE (75.3% vs. 46.8% according to hysteroscopy and 74.0% vs. 33.8% according to histopathology, both with p <.050). The incidence of CE was significantly lower in patients with internal adenomyosis when compared with the other three subgroups. Increased BMI contributed to a higher risk of CE. Conclusions: The prevalence of CE was significantly higher in patients with adenomyosis and infertility. The differences in the incidence of CE are closely associated with the classification of adenomyosis. When patients with infertility are diagnosed with adenomyosis, it is recommended to identify the subtype and screen for endometritis. Summary: The prevalence of CE in patients with adenomyosis and infertility is significantly higher and differences in the incidence of CE are closely associated with the classification of adenomyosis. [ABSTRACT FROM AUTHOR]

Background Local institutional guidelines and order sets were updated in June 2023 to recommend first-line cefoxitin monotherapy for the treatment of intra-amniotic infections (IAIs) and endometritis. This study evaluated the clinical impact of this change. Methods This was a retrospective, observational cohort study in an 11-campus health system comparing clinical outcomes of patients with chorioamnionitis, endometritis, or septic abortion receiving intravenous antimicrobial therapy before and after implementation of first-line cefoxitin monotherapy recommendations for the treatment of these infections. Primary outcome was a composite of serious clinical events postdelivery (ie, intensive care unit admission, death, hospital readmission related to IAI or endometritis within 30 days, additional surgery or procedures, or deep surgical site infection). Baseline characteristics between the pre- and post-cefoxitin groups were compared via Student's t tests for continuous variables and chi-square tests for categorical variables. Outcomes were evaluated via generalized linear modeling. Results A total of 472 patients were enrolled, 350 (74%) in the pre-cefoxitin group and 122 (26%) in the post-cefoxitin group. Groups were significantly different by race, healthcare payor, and hospital campus. Cefoxitin was rarely used in the pre-cefoxitin group (n = 2, <0.1%) and commonly used in the post-cefoxitin group (n = 112, 91.8%). After controlling for group differences, odds of experiencing serious clinical event postdelivery in the post-cefoxitin group were noninferior to those in the pre-cefoxitin group (adjusted odds ratio,.37; 95% CI,.17–.76; P =.010). Conclusions Local institutional guidelines with predominant use of cefoxitin therapy were noninferior to traditional antimicrobial therapy regimens for the treatment of IAI. [ABSTRACT FROM AUTHOR]

Endometritis is one of the important causes of infertility. Puerarin (PU) can inhibit oxidative stress and reduce inflammation; however, it is unclear whether PU has a protective effect on the endometritis. In our study, we used Staphylococcus aureus to induce mouse endometritis. The PU group (100 mg/kg PU) and the S. aureus + PU group received daily intraperitoneal injection of PU (25, 50 or 100 mg/kg PU). The results showed that S. aureus significantly increased the levels of MPO, TNF‐α, IL‐1β and IL‐6 in uterine tissue, and increased the expression of p‐p65 and p‐IκBα proteins in uterine tissue to induce endometritis in mice (p < 0.05). Furthermore, it has been found that S. aureus promotes the occurrence of ferroptosis by reducing GSH and ATP content, increasing MDA and iron content and reducing GPX4 and SLC7A11 protein expression levels (p < 0.05). S. aureus significantly increase the expression of NLRP3, ASC, caspase‐1 and P2X7 proteins in uterine tissue (p < 0.05). However, PU obviously reduced the inflammatory response and reversed the changes of ferroptosis and the expression of P2X7 receptor/NLRP3 pathway associated proteins of the uterus induced by S. aureus (p < 0.05). Taken together, these findings emphasize the protective effect of PU on endometritis by regulating the P2X7 receptor/NLRP3 signalling pathway and inhibiting ferroptosis. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To identify the vaginal microbial signature in women with chronic endometritis (CE) and investigate the potential of vaginal microbiome characterization as a novel diagnostic tools for CE.A cross‐sectional study was conducted to compare the characteristics of the vaginal microbiome in 98 women who underwent endometrial biopsy for routine clinical inspection of infertility (49 women diagnosed with CE and 49 with non‐CE). The vaginal microbiome was analyzed using 16S ribosomal RNA gene amplicon sequencing. The study included an analysis of diversity, bacterial abundance, and microbial function. In addition, microbial markers were identified, and a CE classifier was developed.The relative abundances of genera, including Bifidobacterium, Prevotella and Gardnerella, were found to be different between the two groups. Analysis of the Kyoto Encyclopedia of Genes and Genomes pathways reported differential expression in metabolism‐related pathways in the two groups. We identified four microbial markers of CE (Enterobacter, Prevotella, Faecalibacterium, and Phascolarctobacterium) and developed a predictive classifier for diagnosing CE, achieving an area under the curve of 83.26%.The results of the current study revealed that, compared with the non‐CE controls, patients with CE have a different vaginal microbiota, highlighting the diagnostic significance of the vaginal microbiome as a promising noninvasive biomarker in detecting CE. [ABSTRACT FROM AUTHOR]

Background: The role of bacterial contamination in the development and progression of endometriosis lesions is currently a hot topic for gynecologists. In this study, we decided to compare the endometrial cultures of women affected by endometriosis with those of non-endometriotic women, focusing on specific microbial pathogens. Material and method: In this cross-sectional case-control study, 30 women with endometriosis in stages 4 of the disease whose endometriosis was confirmed based on clinical, ultrasound, and histopathological findings, and 30 women without endometriosis who were candidates for surgery due to benign uterine diseases with regular menstrual cycle, underwent endometrial biopsy with Novak Kort in sterile conditions before starting their operation, and the results of their endometrial culture were analyzed and compared. Results: Results of the study indicate that there were no significant differences in terms of age, BMI, smoking, education level, place of residency, use of the intrauterine device, or vaginal douche, and age of menarche between the case and control groups. The only demographic difference observed was in parity, where the control group had a significantly higher parity than the case group (P = 0.001). Out of the 60 cultures, only 15 samples were positive in the endometriosis group, and E. coli was the most prevalent species, with 10 (33.3%) samples testing positive for it. Klebsiella spp. and Enterobacteria spp. were also detected in 3 (10.0%) and 2 (6.7%) samples, respectively. The comparison between the two groups showed that only E. coli had a significant association with the presence of endometriosis (P = 0.001). There was no significant relationship between the location of endometriosis in the pelvic cavity and culture results. It was observed that parity among the E. coli negative group was significantly higher compared to the E. coli positive group (P < 0.001). Conclusion: Based on The high occurrence of E. coli in women with endometriosis, along with its potential involvement in the progression and/or recurrence of this condition, the researchers propose that treating women with endometriosis and recurrent IVF failure, as well as those with endometriosis recurrence after surgical treatment, with suitable antibiotics and repeated culture until the culture becomes negative, could be beneficial. [ABSTRACT FROM AUTHOR]

Background: Uterine rupture is a rare, but dangerous obstetric complication that can occur during trial of vaginal birth. Methods: The aim of this study was to evaluate the relationship between peripartum infection at the first caesarean delivery to uterine dehiscence or rupture at the subsequent delivery. We conducted a retrospective case-control study from March 2014 to October 2020 at a single academic medical center. The study group included women with a prior caesarean delivery and proven dehiscence or uterine rupture diagnosed during their subsequent delivery. The control group included women who went through a successful vaginal birth after cesarean section (VBAC) without evidence of dehiscence or uterine rupture. We compared the rate of peripartum infection during the first cesarean delivery (CD) and other relevant variables, between the two groups. Results: A total of 168 women were included, 71 with uterine rupture or dehiscence and 97 with successful VBAC as the control group. The rate of peripartum infection at the first caesarean delivery was significantly higher in the study group compared to the control group (22.2% vs. 8.2%, p = 0.013). Multivariate logistic regression analysis found that peripartum infection remained an independent risk factor for uterine rupture at the subsequent trial of labor after CD (95% confidence interval, p = 0.034). Conclusion: Peripartum infection in the first caesarean delivery, may be an independent risk-factor for uterine rupture in a subsequent delivery. [ABSTRACT FROM AUTHOR]

Summary: Background: Bone‐derived exosomes are considered nano‐sized extracellular vesicles secreted by the bone marrow stromal cells. Objectives: This study used exosomes derived from bone marrow mesenchymal stem cells to treat chronic endometritis in Arabian mares with follow‐up alterations in haemodynamics, hormonal and histopathological expressions. Methods and study design: Fourteen (n = 14) Arabian mares (aged 13–15 years old) were equally divided into the control group and an endometritis group (chronic type). Exosomes were infused twice 21 days apart at the first and second ovulations. Follow‐up was done ultrasonographically, and samples were taken for histopathology. Blood samples were taken to estimate hormonal levels. Results: Uterine biopsy samples before treatment showed a marked degree of degeneration, while the second exosomal treatment showed regression of fibrous tissue and restoration of healthy endometrial glands with normal epithelium. Uterine body and horns thickness/mm were decreased after treatment at day 0 of the 3rd ovulation compared to day −1 before treatment, the uterine body‐coloured area and total uterine coloured areas/pixels were elevated (p < 0.05) at day 0 of the 3rd ovulation compared to day −1 before treatment. Uterine artery blood parameters (pulsatility index, resistance index, peak systolic and end‐diastolic points) did not change before, during and after treatment, but the blood flow rate was elevated (p < 0.05) on day 0 of the 3rd ovulation compared to day −1 before treatment. Oestradiol level was decreased (p < 0.05), while progesterone level was increased (p < 0.05) on day 0 of the 3rd ovulation compared to day −1 before treatment. Conclusion: Two intrauterine administrations of exosomes restored the normal endometrial appearance after chronic endometritis resulting in the elevation of the conception rate in infertile mares. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Endometritis is a frequent postpartum disease of dairy cows and inflicts considerable distress on the animals and costs to the dairy industry. This study evaluated the clinical efficacy of Chinese and Western Medicine combination treatments for dairy cow endometritis to provide a reference for the prevention and treatment of these infections. This analysis provides new information for veterinary medical research. We used the keywords ‘Chinese and Western Medicine, Traditional and Western Medicine, Chinese herbs, Traditional Chinese Medicine Traditional Medicine, Chinese, Zhong Yi Xue, Chinese Traditional Medicine, Chinese Medicine, Traditional, Endometritis, Metritis and Cow to assess relevant literature sources collected in CNKI, Wanfang, Vepsa, China Patent Information Network, PubMed, Web of Science and other domestic and foreign databases. We utilized Cochrane system instructions to perform a meta-analysis using RevMan 5. 3 and Stata 16.0 software. We identified 13 randomized clinical trials (RCT) involving 847 dairy cows including cows 435 treated with a combination of Chinese and Western Medicine and 412 cows treated with the Western Medicine approach. The effectiveness for the combination therapy was better than that of the control (antibiotic only) where the relative risk was 1.19 with 95% CI (1.12, 1.26) and Z= 5.96, P<0.01. We found no significant heterogeneity between these studies (I2=0<50%, P= 0.50<0.1) and publication bias was absent as investigated through funnel plots and the Egger regression model (P=0.197>0.05). These results indicated that although the Chinese herbal preparations differed between studies (n= 13), when coupled with Western antibiotic treatments the animals recovered faster than did the control Western antibiotic treatments. These randomized control studies indicated that the efficacy of Chinese and Western Medicine on endometritis in dairy cows is greater than that of Western Medicine treatments. [ABSTRACT FROM AUTHOR]