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Uterine fluid extracellular vesicles (UF-EVs) play a key role in cell-to-cell communication in the uterus, potentially holding the signs of aetiology for endometritis. We used mass spectrometry-based quantitative shotgun proteomics to compare UF-EV proteomic profiles in healthy cows (H), cows with subclinical (SE) or clinical endometritis (CLE) sampled at 28\u201335 days postpartum. Functional analysis was performed on embryo cultures with the exposure to different EV types. A total of 248 UF-EV proteins exhibited differential enrichment between the groups. Interestingly, in SE, EV protein signature suggests a slight suppression of inflammatory response compared to CLE-UF-EVs, clustering closer with healthy cows\u2019 profile. Furthermore, CLE-UF-EVs proteomic profile highlighted pathways associated with cell apoptosis and active inflammation aimed at pathogen elimination. In SE-UF-EVs, the regulation of normal physiological status was aberrant, showing cell damage and endometrial repair at the same time. Serine peptidase HtrA1 (HTRA1) emerged as a potential biomarker for SE. Supplementation of CLE- and SE-derived UF-EVs reduced the embryo developmental rates and quality. Therefore, further research is warranted to elucidate the precise aetiology of SE in cattle, and HTRA1 should be further explored as a potential diagnostic biomarker.<\/jats:p>","DOI":"10.3390\/biom14060626","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T10:14:07Z","timestamp":1716804847000},"page":"626","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Investigation of Uterine Fluid Extracellular Vesicles\u2019 Proteomic Profiles Provides Novel Diagnostic Biomarkers of Bovine Endometritis"],"prefix":"10.3390","volume":"14","author":[{"given":"Johanna","family":"Piibor","sequence":"first","affiliation":[{"name":"Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, Kreutzwaldi 62, 51006 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6903-9638","authenticated-orcid":false,"given":"Andres","family":"Waldmann","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, Kreutzwaldi 62, 51006 Tartu, Estonia"},{"name":"Faculty of Veterinary Medicine, Latvia University of Life Sciences and Technologies, LV-3004 Jelgava, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhusha","family":"Prasadani","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, Kreutzwaldi 62, 51006 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ants","family":"Kavak","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, Kreutzwaldi 62, 51006 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneta","family":"Andronowska","sequence":"additional","affiliation":[{"name":"Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Juliana Tuwima 10, 10-748 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Klein","sequence":"additional","affiliation":[{"name":"Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, H\u00f6ltystr. 10, 31535 Neustadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suranga","family":"Kodithuwakku","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, Kreutzwaldi 62, 51006 Tartu, Estonia"},{"name":"Department of Animal Sciences, Faculty of Agriculture, University of Peradeniya, Peradeniya 20400, Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Fazeli","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, Kreutzwaldi 62, 51006 Tartu, Estonia"},{"name":"Department of Pathophysiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila St. 14b, 50411 Tartu, Estonia"},{"name":"Division of Clinical Medicine, School of Medicine & Population Health, University of Sheffield, Level 4, Jessop Wing, Tree Root Walk, Sheffield S10 2SF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,25]]},"reference":[{"key":"ref_1","first-page":"519","article-title":"Risk factors limiting first service conception rate in dairy cows and their economic impact","volume":"32","author":"Kim","year":"2019","journal-title":"Asian-Australas. 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