{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:23:19Z","timestamp":1792034599385,"version":"4.4.0"},"reference-count":112,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Bovine endometritis remains one of the most significant postpartum uterine disorders. It impairs uterine recovery, compromises fertility, and causes substantial economic losses in dairy production. Growing evidence suggests that the disease cannot be attributed solely to postpartum bacterial contamination; rather, it should be understood as a multifactorial failure to restore uterine homeostasis after calving. This review summarises the latest research findings on six interconnected aspects: the clinical significance of postpartum uterine disease; the diagnostic and biological differences between clinical and subclinical endometritis; the role of microbes in the uterus in health and disease; interactions between the host and uterine bacteria; the mechanisms of persistent inflammatory regulation; and current as well as emerging treatment strategies. Current evidence indicates that postpartum uterine disease is more strongly associated with dysbiosis, reduced microbial diversity, and disturbed microbial succession than with the presence of any single pathogen. Disease progression is driven by complex interplay among microbial ligands, epithelial and stromal immune responses, virulence-associated tissue injury, endocrine disruption, and impaired inflammatory resolution. Furthermore, persistent uterine inflammation is regulated by multilayered networks involving cytokines, prostaglandins, noncoding RNAs, extracellular vesicles, metabolic remodeling, and oxidative stress. Although conventional therapies remain relevant in certain clinical cases, microbiota-oriented approaches, particularly probiotic interventions, have emerged as promising adjunctive strategies for the prevention and control of the condition. Overall, bovine endometritis should be viewed as a disorder caused by disrupted interactions between the host, microbiota and inflammation. Future progress will depend on longitudinal, strain-resolved, and function-oriented studies to enable more precise and less antimicrobial-dependent interventions for postpartum uterine health.<\/jats:p>","DOI":"10.3390\/ani16121860","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T01:58:38Z","timestamp":1781661518000},"page":"1860","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bovine Uterine Microbiota and Endometritis: Ecological Characteristics, Host Interactions, Inflammatory Regulation, and Control Strategies in Dairy Cows"],"prefix":"10.3390","volume":"16","author":[{"given":"Yongqi","family":"Liu","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuaiyu","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.tvjl.2007.12.019","article-title":"Postpartum uterine disease and dairy herd reproductive performance: A review","volume":"176","author":"LeBlanc","year":"2008","journal-title":"Vet. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.anireprosci.2004.04.006","article-title":"Postpartum uterine health in cattle","volume":"82\u201383","author":"Sheldon","year":"2004","journal-title":"Anim. Reprod. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1016\/j.theriogenology.2005.08.021","article-title":"Defining postpartum uterine disease in cattle","volume":"65","author":"Sheldon","year":"2006","journal-title":"Theriogenology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.3168\/jds.S0022-0302(02)74302-6","article-title":"Defining and diagnosing postpartum clinical endometritis and its impact on reproductive performance in dairy cows","volume":"85","author":"LeBlanc","year":"2002","journal-title":"J. Dairy Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"372","DOI":"10.3168\/jds.2012-5584","article-title":"Short communication: Large-scale study on effects of metritis on reproduction in danish holstein cows","volume":"96","author":"Elkjaer","year":"2013","journal-title":"J. Dairy Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1016\/j.theriogenology.2011.07.017","article-title":"Reproductive tract defense and disease in postpartum dairy cows","volume":"76","author":"LeBlanc","year":"2011","journal-title":"Theriogenology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/j.1439-0531.2012.02109.x","article-title":"Interactions of metabolism, inflammation, and reproductive tract health in the postpartum period in dairy cattle","volume":"47","author":"LeBlanc","year":"2012","journal-title":"Reprod. Domest. Anim."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/rda.12205","article-title":"Drivers of post-partum uterine disease in dairy cattle","volume":"48","author":"Williams","year":"2013","journal-title":"Reprod. Domest. Anim."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6511","DOI":"10.3168\/jds.2019-18048","article-title":"Prevalence of endometritis diagnosed by vaginal discharge scoring or uterine cytology in dairy cows and herds","volume":"103","author":"McDougall","year":"2020","journal-title":"J. Dairy Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100781","DOI":"10.1016\/j.animal.2023.100781","article-title":"Review: Postpartum reproductive disease and fertility in dairy cows","volume":"17","author":"LeBlanc","year":"2023","journal-title":"Animal"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"11786","DOI":"10.3168\/jds.2019-17106","article-title":"Symposium review: The uterine microbiome associated with the development of uterine disease in dairy cows","volume":"102","author":"Galvao","year":"2019","journal-title":"J. Dairy Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"R15","DOI":"10.1530\/REP-22-0452","article-title":"Genesis of clinical and subclinical endometritis in dairy cows","volume":"166","author":"LeBlanc","year":"2023","journal-title":"Reproduction"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.theriogenology.2020.01.040","article-title":"Adaptive immunity in the postpartum uterus: Potential use of vaccines to control metritis","volume":"150","author":"Machado","year":"2020","journal-title":"Theriogenology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1146\/annurev-animal-020518-115227","article-title":"Tolerance and innate immunity shape the development of postpartum uterine disease and the impact of endometritis in dairy cattle","volume":"7","author":"Sheldon","year":"2019","journal-title":"Annu. Rev. Anim. Biosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.theriogenology.2003.03.001","article-title":"Endometrial cytology and ultrasonography for the detection of subclinical endometritis in postpartum dairy cows","volume":"62","author":"Kasimanickam","year":"2004","journal-title":"Theriogenology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.theriogenology.2017.02.005","article-title":"A review of the ongoing discussion about definition, diagnosis and pathomechanism of subclinical endometritis in dairy cows","volume":"94","author":"Wagener","year":"2017","journal-title":"Theriogenology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.theriogenology.2007.12.005","article-title":"A comparison of diagnostic techniques for postpartum endometritis in dairy cattle","volume":"69","author":"Barlund","year":"2008","journal-title":"Theriogenology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/j.theriogenology.2010.05.028","article-title":"A clinical approach to determine false positive findings of clinical endometritis by vaginoscopy by the use of uterine bacteriology and cytology in dairy cows","volume":"74","author":"Westermann","year":"2010","journal-title":"Theriogenology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5225","DOI":"10.3168\/jds.2010-3428","article-title":"Definitions and diagnosis of postpartum endometritis in dairy cows","volume":"93","author":"Dubuc","year":"2010","journal-title":"J. Dairy Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6848","DOI":"10.3168\/jds.2014-9120","article-title":"Determination of optimal diagnostic criteria for purulent vaginal discharge and cytological endometritis in dairy cows","volume":"98","author":"Dubuc","year":"2015","journal-title":"J. Dairy Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.theriogenology.2018.08.001","article-title":"Comparison of cow-side diagnostic techniques for subclinical endometritis in dairy cows","volume":"120","author":"Pascottini","year":"2018","journal-title":"Theriogenology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"665","DOI":"10.3168\/jds.2020-20064","article-title":"Cytological endometritis diagnosis in primiparous versus multiparous dairy cows","volume":"105","author":"Druker","year":"2022","journal-title":"J. Dairy Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1111\/rda.12742","article-title":"Distribution of inflammation and association between active and chronic alterations within the endometrium of dairy cows","volume":"51","author":"Pascottini","year":"2016","journal-title":"Reprod. Domest. Anim."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/rda.13367","article-title":"Reproducibility of endometrial cytology using cytobrush technique and agreement for the diagnosis of subclinical endometritis between five predefined endometrial sites","volume":"54","author":"Pothmann","year":"2019","journal-title":"Reprod. Domest. Anim."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Pothmann, H., Flick, P., Tichy, A., Gabler, C., and Drillich, M. (2021). Messenger rna expression of selected factors at different sites of the bovine endometrium associated with uterine health. Front. Vet. Sci., 8.","DOI":"10.3389\/fvets.2021.649758"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/j.1751-0813.2009.00469.x","article-title":"Comparison of two methods of detecting purulent vaginal discharge in postpartum dairy cows and effect of intrauterine cephapirin on reproductive performance","volume":"87","author":"Runciman","year":"2009","journal-title":"Aust. Vet. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1016\/j.theriogenology.2013.02.002","article-title":"Clinical trial of treatment programs for purulent vaginal discharge in lactating dairy cattle in new zealand","volume":"79","author":"McDougall","year":"2013","journal-title":"Theriogenology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3805","DOI":"10.3168\/jds.2016-11373","article-title":"Purulent vaginal discharge in grazing dairy cows: Risk factors, reproductive performance, and prostaglandin f 2\u03b1 treatment","volume":"100","author":"Giuliodori","year":"2017","journal-title":"J. Dairy Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"666","DOI":"10.3168\/jds.2019-17116","article-title":"Purulent vaginal discharge diagnosed in pasture-based holstein-friesian cows at 21 days postpartum is influenced by previous lactation milk yield and results in diminished fertility","volume":"103","author":"Ryan","year":"2020","journal-title":"J. Dairy Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"9778","DOI":"10.3168\/jds.2023-23324","article-title":"Postpartum vaginal discharge score is associated with genetic traits, postpartum fertility phenotypes, metabolic status, and overall reproductive performance in seasonal-calving pasture-based dairy cows","volume":"106","author":"Canadas","year":"2023","journal-title":"J. Dairy Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6079","DOI":"10.3168\/jds.2023-23905","article-title":"Evaluating differences in milk production, reproductive performance, and survival associated with vaginal discharge characteristics and fever in postpartum dairy cows","volume":"107","author":"Figueiredo","year":"2024","journal-title":"J. Dairy Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/j.theriogenology.2010.05.033","article-title":"Prevalence, risk factors for and impact of subclinical endometritis in repeat breeder dairy cows","volume":"74","author":"Salasel","year":"2010","journal-title":"Theriogenology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.3168\/jds.2010-3758","article-title":"Effects of postpartum uterine diseases on milk production and culling in dairy cows","volume":"94","author":"Dubuc","year":"2011","journal-title":"J. Dairy Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5764","DOI":"10.3168\/jds.2010-3429","article-title":"Risk factors for postpartum uterine diseases in dairy cows","volume":"93","author":"Dubuc","year":"2010","journal-title":"J. Dairy Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5682","DOI":"10.3168\/jds.2012-6335","article-title":"Prevalence of periparturient diseases and effects on fertility of seasonally calving grazing dairy cows supplemented with concentrates","volume":"96","author":"Ribeiro","year":"2013","journal-title":"J. Dairy Sci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Bruinje, T.C., and LeBlanc, S.J. (2025). Invited review: Inflammation and health in the transition period influence reproductive function in dairy cows. Animals, 15.","DOI":"10.3390\/ani15050633"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8380","DOI":"10.3168\/jds.2021-20330","article-title":"Invited review: The influence of immune activation on transition cow health and performance-a critical evaluation of traditional dogmas","volume":"104","author":"Horst","year":"2021","journal-title":"J. Dairy Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3983","DOI":"10.3168\/jds.2013-7450","article-title":"Invited review: Systematic review of diagnostic tests for reproductive-tract infection and inflammation in dairy cows","volume":"97","author":"LeBlanc","year":"2014","journal-title":"J. Dairy Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4953","DOI":"10.3168\/jds.2017-12592","article-title":"Hot topic: 16s rrna gene sequencing reveals the microbiome of the virgin and pregnant bovine uterus","volume":"100","author":"Moore","year":"2017","journal-title":"J. Dairy Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.theriogenology.2016.02.016","article-title":"An investigation of the microbiota in uterine flush samples and endometrial biopsies from dairy cows during the first 7 weeks postpartum","volume":"86","author":"Knudsen","year":"2016","journal-title":"Theriogenology"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Becker, A.A.M.J., Munden, S., McCabe, E., Hurley, D., Fanning, S., Chapwanya, A., and Butaye, P. (2023). The endometrial microbiota-16s rrna gene sequence signatures in healthy, pregnant and endometritis dairy cows. Vet. Sci., 10.","DOI":"10.3390\/vetsci10030215"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6324","DOI":"10.1128\/AEM.01753-15","article-title":"Uterine microbiota progression from calving until establishment of metritis in dairy cows","volume":"81","author":"Jeon","year":"2015","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Miranda-CasoLuengo, R., Lu, J., Williams, E.J., Miranda-CasoLuengo, A.A., Carrington, S.D., Evans, A.C.O., and Meijer, W.G. (2019). Delayed differentiation of vaginal and uterine microbiomes in dairy cows developing postpartum endometritis. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0200974"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.theriogenology.2023.09.016","article-title":"Uterine microbial ecology and disease in cattle: A review","volume":"213","author":"Comlekcioglu","year":"2024","journal-title":"Theriogenology"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Santos, T.M.A., and Bicalho, R.C. (2012). Diversity and succession of bacterial communities in the uterine fluid of postpartum metritic, endometritic and healthy dairy cows. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0053048"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3850","DOI":"10.3168\/jds.2016-12058","article-title":"Genetic and functional analysis of the bovine uterine microbiota. Part i: Metritis versus healthy cows","volume":"100","author":"Bicalho","year":"2017","journal-title":"J. Dairy Sci."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"He, X., Wang, J., Jiang, L., Wang, X., Wang, Y., Liu, Y., Cheng, Y., Xu, F., and Li, X. (2025). Uterine microbiota composition in dairy cows with different vaginal discharge scores: Suggesting caviibacter as a potential pathogen in mild purulent metritis. Microorganisms, 13.","DOI":"10.3390\/microorganisms13081728"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s42523-023-00281-5","article-title":"Unveiling the microbiome during post-partum uterine infection: A deep shotgun sequencing approach to characterize the dairy cow uterine microbiome","volume":"5","author":"Basbas","year":"2023","journal-title":"Anim. Microbiome"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Wang, M., Liu, M., Xu, J., An, L., Wang, J., and Zhu, Y. (2018). Uterine microbiota of dairy cows with clinical and subclinical endometritis. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.02691"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"18274","DOI":"10.1038\/s41598-025-03265-4","article-title":"Shotgun metagenomic composition, microbial interactions and functional insights into the uterine microbiome of postpartum dairy cows with clinical and subclinical endometritis","volume":"15","author":"Rashid","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"12353","DOI":"10.1038\/s41598-020-69317-z","article-title":"Dynamics of uterine microbiota in postpartum dairy cows with clinical or subclinical endometritis","volume":"10","author":"Pascottini","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s40168-025-02264-x","article-title":"Integrated metagenomic and metabolomic analyses reveal tenacissoside g as a potential non-antimicrobial treatment for bovine endometritis","volume":"14","author":"Cao","year":"2025","journal-title":"Microbiome"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Gupta, D., Sarkar, A., Pal, Y., Suthar, V., Chawade, A., and Kushwaha, S.K. (2024). Bovine reproductive tract and microbiome dynamics: Current knowledge, challenges, and its potential to enhance fertility in dairy cows. Front. Microbiomes, 3.","DOI":"10.3389\/frmbi.2024.1473076"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.theriogenology.2020.01.017","article-title":"Preventing postpartum uterine disease in dairy cattle depends on avoiding, tolerating and resisting pathogenic bacteria","volume":"150","author":"Sheldon","year":"2020","journal-title":"Theriogenology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1210\/en.2005-1113","article-title":"Expression and function of toll-like receptor 4 in the endometrial cells of the uterus","volume":"147","author":"Herath","year":"2006","journal-title":"Endocrinology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1095\/biolreprod.111.092718","article-title":"Toll-like receptor 4 and myd88-dependent signaling mechanisms of the innate immune system are essential for the response to lipopolysaccharide by epithelial and stromal cells of the bovine endometrium","volume":"86","author":"Cronin","year":"2012","journal-title":"Biol. Reprod."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1210\/en.2013-1822","article-title":"Epithelial and stromal cells of bovine endometrium have roles in innate immunity and initiate inflammatory responses to bacterial lipopeptides in vitro via toll-like receptors tlr2, tlr1, and tlr6","volume":"155","author":"Turner","year":"2014","journal-title":"Endocrinology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1095\/biolreprod.115.127936","article-title":"Polarized epithelial cells secrete interleukin 6 apically in the bovine endometrium","volume":"92","author":"Healy","year":"2015","journal-title":"Biol. Reprod."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1038\/mi.2015.131","article-title":"Signal transducer and activator of transcription-3 licenses toll-like receptor 4-dependent interleukin (il)-6 and il-8 production via il-6 receptor-positive feedback in endometrial cells","volume":"9","author":"Cronin","year":"2016","journal-title":"Mucosal Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1210\/en.2008-1379","article-title":"Bacterial lipopolysaccharide induces an endocrine switch from prostaglandin f2alpha to prostaglandin e2 in bovine endometrium","volume":"150","author":"Herath","year":"2009","journal-title":"Endocrinology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.plefa.2018.01.004","article-title":"Pge(2) downregulates lps-induced inflammatory responses via the tlr4-nf-kappab signaling pathway in bovine endometrial epithelial cells","volume":"129","author":"Shen","year":"2018","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/1477-7827-6-53","article-title":"Toll-like receptor and antimicrobial peptide expression in the bovine endometrium","volume":"6","author":"Davies","year":"2008","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1016\/j.theriogenology.2016.06.022","article-title":"Increased mrna expression of selected antimicrobial peptides around ovulation and during inflammatory processes in the bovine endometrium postpartum","volume":"86","author":"Ibrahim","year":"2016","journal-title":"Theriogenology"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Ibrahim, M., Peter, S., Wagener, K., Drillich, M., Ehling-Schulz, M., Einspanier, R., and Gabler, C. (2017). Bovine endometrial epithelial cells scale their pro-inflammatory response in vitro to pathogenic trueperella pyogenes isolated from the bovine uterus in a strain-specific manner. Front. Cell. Infect. Microbiol., 7.","DOI":"10.3389\/fcimb.2017.00264"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.vetmic.2011.11.034","article-title":"Association between virulence factors of Escherichia coli, fusobacterium necrophorum, and arcanobacterium pyogenes and uterine diseases of dairy cows","volume":"157","author":"Bicalho","year":"2012","journal-title":"Vet. Microbiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/j.theriogenology.2015.07.004","article-title":"Effects of intrauterine infusion of trueperella pyogenes on endometrial mrna expression of proinflammatory cytokines and luteolytic cascade genes and their association with luteal life span in dairy cows","volume":"84","author":"Lima","year":"2015","journal-title":"Theriogenology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1095\/biolreprod.113.115972","article-title":"Differential endometrial cell sensitivity to a cholesterol-dependent cytolysin links trueperella pyogenes to uterine disease in cattle","volume":"90","author":"Amos","year":"2014","journal-title":"Biol. Reprod."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7060","DOI":"10.1038\/srep07060","article-title":"Endometrial cells sense and react to tissue damage during infection of the bovine endometrium via interleukin 1","volume":"4","author":"Healy","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1093\/biolre\/ioy099","article-title":"Isoprenoids increase bovine endometrial stromal cell tolerance to the cholesterol-dependent cytolysin from trueperella pyogenes","volume":"99","author":"Griffin","year":"2018","journal-title":"Biol. Reprod."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e21889","DOI":"10.1096\/fj.202100036R","article-title":"Oxysterols protect bovine endometrial cells against pore-forming toxins from pathogenic bacteria","volume":"35","author":"Ormsby","year":"2021","journal-title":"FASEB J."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Ma, X., Li, Y., Shen, W., Oladejo, A.O., Yang, J., Jiang, W., Imam, B.H., Wu, X., Ding, X., and Yang, Y. (2021). Lps mediates bovine endometrial epithelial cell pyroptosis directly through both nlrp3 classical and non-classical inflammasome pathways. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.676088"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Shen, W., Ma, X., Shao, D., Wu, X., Wang, S., Zheng, J., Lv, Y., Ding, X., Ma, B., and Yan, Z. (2022). Neutrophil extracellular traps mediate bovine endometrial epithelial cell pyroptosis in dairy cows with endometritis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232214013"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1093\/biolre\/ioae067","article-title":"Metritis and the uterine disease microbiome are associated with long-term changes in the endometrium of dairy cows","volume":"111","author":"Silva","year":"2024","journal-title":"Biol. Reprod."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"13958","DOI":"10.3168\/jds.2025-26403","article-title":"Evaluating differences in uterine microbiome and inflammatory status at 1 month postpartum associated with metritis and antibiotic treatment","volume":"108","author":"Moraes","year":"2025","journal-title":"J. Dairy Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"11864","DOI":"10.1038\/s41598-024-61704-0","article-title":"Shifts in uterine microbiome associated with pregnancy outcomes at first insemination and clinical cure in dairy cows with metritis","volume":"14","author":"Figueiredo","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1093\/biolre\/ioaf038","article-title":"Differences in uterine and serum metabolome associated with clinical cure failure of metritis in dairy cows","volume":"112","author":"Pereira","year":"2025","journal-title":"Biol. Reprod."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1530\/REP-19-0564","article-title":"Uterine infection alters the transcriptome of the bovine reproductive tract three months later","volume":"160","author":"Horlock","year":"2020","journal-title":"Reproduction"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Dickson, M.J., Bishop, J., Hansen, T.R., Sheldon, I.M., and Bromfield, J.J. (2022). The endometrial transcriptomic response to pregnancy is altered in cows after uterine infection. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0265062"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"107460","DOI":"10.1016\/j.anireprosci.2024.107460","article-title":"Analysis of blood biochemistry and non-targeted metabolomics of endometritis in dairy cows","volume":"264","author":"Ji","year":"2024","journal-title":"Anim. Reprod. Sci."},{"key":"ref_80","first-page":"100","article-title":"Global transcriptomic profiling of bovine endometrial immune response in vitro. I. Effect of lipopolysaccharide on innate immunity","volume":"93","author":"Oguejiofor","year":"2015","journal-title":"Biol. Reprod."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Guo, Y., van Schaik, T., Jhamat, N., Niazi, A., Chanrot, M., Charpigny, G., Valarcher, J.F., Bongcam-Rudloff, E., Andersson, G., and Humblot, P. (2019). Differential gene expression in bovine endometrial epithelial cells after challenge with lps; Specific implications for genes involved in embryo maternal interactions. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0222081"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Ding, X., Lv, H., Deng, L., Hu, W., Peng, Z., Yan, C., Yang, D., Tong, C., and Wang, X. (2020). Analysis of transcriptomic changes in bovine endometrial stromal cells treated with lipopolysaccharide. Front. Vet. Sci., 7.","DOI":"10.3389\/fvets.2020.575865"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e13676","DOI":"10.14814\/phy2.13676","article-title":"Regulation of inflammatory mediator expression in bovine endometrial cells: Effects of lipopolysaccharide, interleukin 1 beta, and tumor necrosis factor alpha","volume":"6","author":"Koh","year":"2018","journal-title":"Physiol. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.theriogenology.2020.04.004","article-title":"Tlr2 \/ 4 promotes pge 2 production to increase tissue damage in Escherichia coli\u2014Infected bovine endometrial explants via myd88 \/ p38 mapk pathway","volume":"152","author":"Li","year":"2020","journal-title":"Theriogenology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"117374","DOI":"10.1016\/j.theriogenology.2025.117374","article-title":"Dual roles of the tlr2\/tlr4\/nlrp3-h-pgds-pgd2 axis in regulating the inflammatory response in Escherichia coli-infected bovine bone marrow-derived macrophages and endometrial tissue","volume":"239","author":"Yang","year":"2025","journal-title":"Theriogenology"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.theriogenology.2014.04.022","article-title":"Inflammatory cytokine concentrations in uterine flush and serum samples from dairy cows with clinical or subclinical endometritis","volume":"82","author":"Kim","year":"2014","journal-title":"Theriogenology"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s11259-015-9635-4","article-title":"Inflammatory cytokine and acute phase protein concentrations in the peripheral blood and uterine washings of cows with subclinical endometritis in the late postpartum period","volume":"39","author":"Brodzki","year":"2015","journal-title":"Vet. Res. Commun."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Salilew-Wondim, D., Ibrahim, S., Gebremedhn, S., Tesfaye, D., Heppelmann, M., Bollwein, H., Pfarrer, C., Tholen, E., Neuhoff, C., and Schellander, K. (2016). Clinical and subclinical endometritis induced alterations in bovine endometrial transcriptome and mirnome profile. BMC Genom., 17.","DOI":"10.1186\/s12864-016-2513-9"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"6125","DOI":"10.3168\/jds.2022-21811","article-title":"Subclinical endometritis differentially affects the transcriptomic profiles of endometrial glandular, luminal, and stromal cells of postpartum dairy cows","volume":"105","author":"Perelra","year":"2022","journal-title":"J. Dairy Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"9704","DOI":"10.3168\/jds.2023-23616","article-title":"Characterization of circulating microrna profiles of postpartum dairy cows with persistent subclinical endometritis","volume":"106","author":"Pereira","year":"2023","journal-title":"J. Dairy Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"18050","DOI":"10.1038\/s41598-021-97319-y","article-title":"An integrated analysis of mrnas, lncrnas, and mirnas based on weighted gene co-expression network analysis involved in bovine endometritis","volume":"11","author":"Sheybani","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Kasimanickam, R., Ferreira, J., and Kasimanickam, V. (2025). Integrative analysis of differentially expressed mirnas and noncoding rna networks reveals molecular mechanisms underlying metritis in postpartum dairy cows. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47080643"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1111\/1751-7915.13565","article-title":"Exosome\u2014Derived uterine mir\u2014218 isolated from cows with endometritis regulates the release of cytokines and chemokines","volume":"13","author":"Wang","year":"2020","journal-title":"Microb. Biotechnol."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Zhao, G., Jiang, K., Yang, Y., Zhang, T., Wu, H., Shaukat, A., Qiu, C., and Deng, G. (2018). The potential therapeutic role of mir-223 in bovine endometritis by targeting the nlrp3 inflammasome. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01916"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"9143","DOI":"10.3168\/jds.2017-13261","article-title":"Effect of exosomes from plasma of dairy cows with or without an infected uterus on prostaglandin production by endometrial cell lines","volume":"100","author":"Almughlliq","year":"2017","journal-title":"J. Dairy Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"5425","DOI":"10.1038\/s41598-023-32045-1","article-title":"Dynamics of inflammatory cytokine expression in bovine endometrial cells exposed to cow blood plasma small extracellular vesicles (sev) may reflect high fertility","volume":"13","author":"Abeysinghe","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/1477-7827-11-103","article-title":"Associations among serum pro\u2014And anti-inflammatory cytokines, metabolic mediators, body condition, and uterine disease in postpartum dairy cows","volume":"11","author":"Kasimanickam","year":"2013","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.rvsc.2021.07.006","article-title":"Metabolomic analysis of untargeted bovine uterine secretions in dairy cows with endometritis using ultra-performance liquid chromatography\/quadrupole time-of-flight mass spectrometry","volume":"139","author":"Wang","year":"2021","journal-title":"Res. Vet. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"de Oliveira, E.B., Monteiro, H.F., Pereira, J.M.V., Williams, D.R., Pereira, R.V., Rio, N.S.D., Menta, P.R., Machado, V.S., and Lima, F.S. (2023). Changes in uterine metabolome associated with metritis development and cure in lactating holstein cows. Metabolites, 13.","DOI":"10.3390\/metabo13111156"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Song, P., Liu, C., Sun, M., Liu, J., Lin, P., Wang, A., and Jin, Y. (2022). Oxidative stress induces bovine endometrial epithelial cell damage through mitochondria-dependent pathways. Animals, 12.","DOI":"10.3390\/ani12182444"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Song, P., Sun, M., Liu, C., Liu, J., Lin, P., Chen, H., Zhou, D., Tang, K., Wang, A., and Jin, Y. (2023). Reactive oxygen species damage bovine endometrial epithelial cells via the cytochrome c-mptp pathway. Antioxidants, 12.","DOI":"10.3390\/antiox12122123"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Liu, J., Qiu, R., Liu, R., Song, P., Lin, P., Chen, H., Zhou, D., Wang, A., and Jin, Y. (2022). Autophagy mediates Escherichia coli\u2014Induced cellular inflammatory injury by regulating calcium mobilization, mitochondrial dysfunction, and endoplasmic reticulum stress. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232214174"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.3168\/jds.S0022-0302(02)74303-8","article-title":"The effect of treatment of clinical endometritis on reproductive performance in dairy cows","volume":"85","author":"LeBlanc","year":"2002","journal-title":"J. Dairy Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"10557","DOI":"10.3168\/jds.2018-14933","article-title":"Short communication: Meta-analysis on therapy of bovine endometritis with prostaglandin f 2\u03b1\u2014An update","volume":"101","author":"Haimerl","year":"2018","journal-title":"J. Dairy Sci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.theriogenology.2015.09.054","article-title":"Potential of lactic acid bacteria at regulating Escherichia coli infection and inflammation of bovine endometrium","volume":"85","author":"Genis","year":"2016","journal-title":"Theriogenology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"479","DOI":"10.3168\/jds.2016-11671","article-title":"A combination of lactic acid bacteria regulates escherichia coil infection and inflammation of the bovine endometrium","volume":"100","author":"Genis","year":"2017","journal-title":"J. Dairy Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.vetmic.2017.04.025","article-title":"Effects of intravaginal lactic acid bacteria on bovine endometrium: Implications in uterine health","volume":"204","author":"Genis","year":"2017","journal-title":"Vet. Microbiol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"6018","DOI":"10.3168\/jds.2014-8559","article-title":"Intravaginally administered lactic acid bacteria expedited uterine involution and modulated hormonal profiles of transition dairy cows","volume":"98","author":"Deng","year":"2015","journal-title":"J. Dairy Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.rvsc.2014.02.007","article-title":"Intravaginal administration of lactic acid bacteria modulated the incidence of purulent vaginal discharges, plasma haptoglobin concentrations, and milk production in dairy cows","volume":"96","author":"Ametaj","year":"2014","journal-title":"Res. Vet. Sci."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Genis, S., Cerri, R.L.A., Bach, A., Silper, B.F., Baylao, M., Denis-Robichaud, J., and Aris, A. (2018). Pre\u2014Calving intravaginal administration of lactic acid bacteria reduces metritis prevalence and regulates blood neutrophil gene expression after calving in dairy cattle. Front. Vet. Sci., 5.","DOI":"10.3389\/fvets.2018.00135"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"5473","DOI":"10.1038\/s41598-018-22856-y","article-title":"Influence of intrauterine administration of lactobacillus buchneri on reproductive performance and pro-inflammatory endometrial mrna expression of cows with subclinical endometritis","volume":"8","author":"Peter","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"4860","DOI":"10.3168\/jds.2022-22147","article-title":"Use of intravaginal lactic acid bacteria prepartum as an approach for preventing uterine disease and its association with fertility of lactating dairy cows","volume":"106","author":"Madureira","year":"2023","journal-title":"J. Dairy Sci."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/12\/1860\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T04:25:08Z","timestamp":1782102308000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/12\/1860"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,16]]},"references-count":112,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ani16121860"],"URL":"https:\/\/doi.org\/10.3390\/ani16121860","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,16]]}}}