{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:12:44Z","timestamp":1788415964843,"version":"build-2803163510"},"reference-count":103,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Seminal plasma (SP) is a complex immune modulator within the female reproductive tract of several species. In sheep, it can restore the fertility of cryopreserved sperm and is necessary for the fertility of epididymal sperm following cervical artificial insemination. We have also shown it capable of protecting cryopreserved sperm from polymorphonuclear leukocyte (PMN) binding\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Thus, we hypothesize SP, and its components confer immune protection to sperm following deposition in the ovine cervix and that sperm cryopreservation disrupts this delicate sperm-female interaction. To delineate the contributions of soluble and extracellular vesicle (EV) associated SP components, frozen-thawed ram spermatozoa were incubated with whole SP, EV-depleted SP (DSP) and enriched EVs. All SP treatments significantly reduced binding (FTSP: 20.7 \u00b1 3.39%; FTDSP: 24.3 \u00b1 3.64%; FTEV: 19.8 \u00b1 3.63%) compared to the control (36.3 \u00b1 3.63%; p &amp;lt; 0.0001), with no differences between treated groups. To further isolate inhibitory factors, FT was incubated with SP fractionated into 5 molecular weight treatments (F1\n                    <jats:sup>-5<\/jats:sup>\n                    ; &amp;lt;10, 10\u201330, 30\u201350, 50\u2013100, &amp;gt;100 kDa). Two fractions, F3 (30\n                    <jats:sup>-5<\/jats:sup>\n                    0kDa) and F5 (&amp;gt;100kDa) reduced PMN binding (22.44 \u00b1 2.18%, 21.67 \u00b1 1.85%, respectively) compared to the control (FT: 58.83 \u00b1 4.54%; p &amp;lt; 0.0001) and similar to whole SP (20.67 \u00b1 1.65%; p&amp;gt;0.05), indicating these fractions contain key immunoregulatory factors. Proteomic analysis identified 2,161 proteins in whole SP, with SP-EVs contributing 795 unique proteins. Among protective fractions (SP, DSP, EV, F3, F5), 588 proteins were shared, including a core signature of PITPNB, RPLP2, SLC9A3R1, PTTG1IP, CKAP4, and FKBP11, absent in non-protective fractions. Complement regulators (CD46, CD59, CFH, CLU) and glycocalyx-associated proteins (CRISPs, DEFB124) were enriched in protective fractions, supporting layered immunomodulation via both soluble and vesicular delivery. Functional analyses demonstrated that SP modulates PMN binding and activation while maintaining sperm viability, highlighting a structured, multi-layered immunoregulatory system. These findings provide the most comprehensive characterization of ram SP and SP-EVs to date, integrating functional assays with proteomic profiling, and reveal conserved protein signatures that underpin sperm immune tolerance. This work establishes a foundation for future studies targeting EV-mediated delivery and glycocalyx-associated immunoregulators to improve fertility outcomes and assisted reproductive technologies.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1891264","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:15:37Z","timestamp":1788412537000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterisation of seminal plasma-derived mediators involved in PMN evasion of ram spermatozoa in vitro"],"prefix":"10.3389","volume":"17","author":[{"given":"Sophie","family":"Warr","sequence":"first","affiliation":[{"name":"School of Life and Environmental Sciences, Faculty of Science, The University of Sydney","place":["Sydney, NSW, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Mikhael","sequence":"additional","affiliation":[{"name":"School of Life and Environmental Sciences, Faculty of Science, The University of Sydney","place":["Sydney, NSW, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Torres-Arce","sequence":"additional","affiliation":[{"name":"Centre for Reproductive Science, School of Science, College of Engineering, Science and Environment, University of Newcastle, University Drive","place":["Callaghan, NSW, Australia"]},{"name":"Reproductive and Family Health Research Program, Hunter Medical Research Institute","place":["New Lambton Heights, NSW, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Schjenken","sequence":"additional","affiliation":[{"name":"Centre for Reproductive Science, School of Science, College of Engineering, Science and Environment, University of Newcastle, University Drive","place":["Callaghan, NSW, Australia"]},{"name":"Reproductive and Family Health Research Program, Hunter Medical Research Institute","place":["New Lambton Heights, NSW, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Pini","sequence":"additional","affiliation":[{"name":"School of Veterinary Science, Faculty of Science, The University of Queensland","place":["Gatton, QLD, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon P.","family":"de Graaf","sequence":"additional","affiliation":[{"name":"School of Life and Environmental Sciences, Faculty of Science, The University of Sydney","place":["Sydney, NSW, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica P.","family":"Rickard","sequence":"additional","affiliation":[{"name":"School of Life and Environmental Sciences, Faculty of Science, The University of Sydney","place":["Sydney, NSW, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-47446-5_8","article-title":"Molecular insights to the sperm\u2013cervix interaction and the consequences for cryopreserved sperm","volume":"108","author":"Warr","year":"2023","journal-title":"Biol Reprod"},{"key":"B2","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/s0378-4320(00)00155-x","article-title":"Storage of ram semen","volume":"62","author":"Salamon","year":"2000","journal-title":"Anim Reprod Sci"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0220399","article-title":"Fertility of ram spermatozoa frozen by the pellet method","volume":"22","author":"Lightfoot","year":"1970","journal-title":"J Reprod Fertility"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1017\/s0021859600061906","article-title":"A comparison of vaginal, cervical and intrauterine insemination of sheep","volume":"106","author":"Maxwell","year":"1986","journal-title":"J Agric Sci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1530\/biosciprocs.4.021","article-title":"The functional integrity and fate of cryopreserved ram spermatozoa in the female tract","volume":"54","author":"Gillan","year":"1999","journal-title":"J Reprod Fertil Suppl"},{"key":"B6","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.theriogenology.2018.06.006","article-title":"Sublethal sperm freezing damage: Manifestations and solutions","volume":"181","author":"Pini","year":"2018","journal-title":"Theriogenology"},{"key":"B7","first-page":"cwaf067","article-title":"Sialidases derived from Gardnerella vaginalis and Prevotella timonensis remodel the sperm glycocalyx and impair sperm function","volume-title":"Glycobiology","author":"Dohadwala","year":"2025"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1071\/rd99046","article-title":"Normal fertility in ewes after cervical insemination with frozen\u2013thawed spermatozoa supplemented with seminal plasma","volume":"11","author":"Maxwell","year":"1999","journal-title":"Reprod Fertil Dev"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1530\/rep-14-0285e","article-title":"Seminal plasma aids the survival and cervical transit of epididymal ram spermatozoa","volume":"148","author":"Rickard","year":"2014","journal-title":"Reproduction"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nri2873","article-title":"Sterile inflammation: sensing and reacting to damage","volume":"10","author":"Chen","year":"2010","journal-title":"Nat Rev Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2004.01898.x","article-title":"Toll\u2010like receptor (TLR) expression and TLR\u2010mediated cytokine\/chemokine production by human uterine epithelial cells","volume":"112","author":"Schaefer","year":"2004","journal-title":"Immunology"},{"key":"B12","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1111\/j.1439-0531.2012.02120.x","article-title":"Post\u2010mating inflammatory responses of the uterus","volume":"47","author":"Katila","year":"2012","journal-title":"Reprod Domest Anim"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1530\/rep.0.1250357","article-title":"Neutrophil recruitment and phagocytosis of boar spermatozoa after artificial insemination of sows, and the effects of inseminate volume, sperm dose and specific additives in the extender","volume":"125","author":"Matthijs","year":"2003","journal-title":"Reproduction"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1071\/rd05165","article-title":"Leucocyte population changes in the reproductive tract of the ewe in response to insemination","volume":"18","author":"Scott","year":"2006","journal-title":"Reprod Fertil Dev"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102736","article-title":"Seminal fluid induces leukocyte recruitment and cytokine and chemokine mRNA expression in the human cervix after coitus","volume":"188","author":"Sharkey","year":"2012","journal-title":"J Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00013.2018","article-title":"The female response to seminal fluid","volume":"100","author":"Schjenken","year":"2020","journal-title":"Physiol Rev"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.1992.tb00765.x","article-title":"The leukocytic reaction of the human uterine cervix","volume":"28","author":"Thompson","year":"1992","journal-title":"Am J Reprod Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.50.3.252","article-title":"Determination of the number and distribution of macrophages, lymphocytes, and granulocytes in the mouse uterus from mating through implantation","volume":"50","author":"De","year":"1991","journal-title":"J Leukocyte Biol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0060305","article-title":"Spermatozoan transport and leucocytic responses in the reproductive tract of calves","volume":"6","author":"Howe","year":"1963","journal-title":"Reproduction"},{"key":"B20","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1530\/jrf.0.0180297","article-title":"Differential leucocytic responses to spermatozoa in the cervix and the uterus in ewes","volume":"18","author":"Mattner","year":"1969","journal-title":"Reproduction"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.1140195","article-title":"Characterization of uterine leukocyte infiltration in gilts after artificial insemination","volume":"114","author":"Rozeboom","year":"1998","journal-title":"Reproduction"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/biolreprod\/52.monograph_series1.515","article-title":"Onset and duration of uterine inflammatory response of mares after insemination with fresh semen","volume":"52","author":"Katila","year":"1995","journal-title":"Biol Reprod"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1071\/RD09012","article-title":"Spermatozoa and seminal plasma induce a greater inflammatory response in the ovine uterus at oestrus than dioestrus","volume":"21","author":"Scott","year":"2009","journal-title":"Reprod Fertil Dev"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00113","article-title":"Neutrophil: a cell with many roles in inflammation or several cell types","volume":"9","author":"Rosales","year":"2018","journal-title":"Front Physiol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.1992.tb00742.x","article-title":"The complement system in human reproduction","volume":"27","author":"Vanderpuye","year":"1992","journal-title":"Am J Reprod Immunol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1002\/(sici)1097-0185(199609)246:1<78::aid-ar9>3.0.co;2-b","article-title":"Human complement regulator expression by the normal female reproductive tract","volume":"246","author":"Oglesby","year":"1996","journal-title":"Anat Rec"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.083001.084359","article-title":"Innate immune recognition","volume":"20","author":"Janewa","year":"2002","journal-title":"Annu Rev Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.anireprosci.2008.10.015","article-title":"Species-specific interaction of seminal plasma on sperm-neutrophil binding.","volume":"114","author":"Alghamdi","year":"2009","journal-title":"Anim Reprod Sci."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.theriogenology.2021.09.012","article-title":"Comparison of the uterine inflammatory response to frozen-thawed sperm from high and low fertility bulls","volume":"176","author":"Donnellan","year":"2021","journal-title":"Theriogenology"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.110.084491","article-title":"Equine CRISP3 modulates interaction between spermatozoa and polymorphonuclear neutrophils1","volume":"85","author":"Doty","year":"2011","journal-title":"Biol Reprod"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioad031","article-title":"The transcriptomic response of bovine uterine tissue is altered in response to sperm from high-and low-fertility bulls","volume":"108","author":"Donnellan","year":"2023","journal-title":"Biol Reprod"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2021.103339","article-title":"Swine spermatozoa trigger aggregated neutrophil extracellular traps leading to adverse effects on sperm function","volume":"146","author":"Zambrano","year":"2021","journal-title":"J Reprod Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3390\/antiox14070778","article-title":"Modulation of NETosis in swine neutrophil\u2013spermatozoa co-cultures in vitro: Effects of butylated hydroxytoluene, albumin, prostaglandin E2, and seminal plasma","volume":"14","author":"Zambrano","year":"2025","journal-title":"Antioxidants"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1111\/evj.13457","article-title":"Seminal plasma, and not sperm, induces time and concentration-dependent neutrophil extracellular trap release in donkeys","volume":"54","author":"Mateo-Otero","year":"2022","journal-title":"Equine Vet J"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2016.06.005","article-title":"Leukocytes coincubated with human sperm trigger classic neutrophil extracellular traps formation, reducing sperm motility","volume":"106","author":"Zambrano","year":"2016","journal-title":"Fertil Steril"},{"key":"B36","doi-asserted-by":"publisher","first-page":"RD25131","DOI":"10.1071\/rd25131","article-title":"Evaluating sperm\u2013polymorphonuclear leukocyte interactions in vitro: the immunomodulatory role of seminal plasma and implications for future ovine studies","volume":"38","author":"Mikhael","year":"2026","journal-title":"Reprod Fertil Dev"},{"key":"B37","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1071\/rd17251","article-title":"Seminal plasma and cryopreservation alter ram sperm surface carbohydrates and interactions with neutrophils","volume":"30","author":"Pini","year":"2018","journal-title":"Reprod Fertil Dev"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1530\/rep-24-0465","article-title":"Seminal plasma protects frozen-thawed ram spermatozoa from neutrophil attack: a complement mediated dynamic","volume":"170","author":"Warr","year":"2025","journal-title":"Reproduction"},{"key":"B39","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1530\/rep.1.00096","article-title":"Equine seminal plasma reduces sperm binding to polymorphonuclear neutrophils (PMNs) and improves the fertility of fresh semen inseminated into inflamed uteri","volume":"127","author":"Alghamdi","year":"2004","journal-title":"Reproduction"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.anireprosci.2005.07.005","article-title":"Components in seminal plasma regulating sperm transport and elimination","volume":"89","author":"Troedsson","year":"2005","journal-title":"Anim Reprod Sci"},{"key":"B41","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.theriogenology.2011.07.018","article-title":"Boar seminal plasma or hen's egg yolk decrease the in-vitro chemotactic and phagocytotic activities of neutrophils when co-incubated with boar or bull sperm","volume":"77","author":"Li","year":"2012","journal-title":"Theriogenology"},{"key":"B42","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/978-3-642-01379-9_3","article-title":"Sperm surface proteomics","volume-title":"Immune Infertility: The Impact of Immune Reactions on Human Infertility","author":"Gadella","year":"2009"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1530\/REP-18-0627","article-title":"Ram seminal plasma and its functional proteomic assessment","volume":"157","author":"Leahy","year":"2019","journal-title":"Reproduction"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201900289","article-title":"Quantitative proteomic analysis of seminal plasma, sperm membrane proteins, and seminal extracellular vesicles suggests vesicular mechanisms aid in the removal and addition of proteins to the ram sperm membrane","volume":"20","author":"Leahy","year":"2020","journal-title":"Proteomics"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1530\/raf-23-0088","article-title":"The efficacy and functional consequences of interactions between human spermatozoa and seminal fluid extracellular vesicles","volume":"5","author":"Tamessar","year":"2024","journal-title":"Reprod Fertility"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/reprod\/xaaf006","article-title":"Exploring the contributions of human seminal extracellular vesicles to reproduction and fertility","volume":"171","author":"Torres-Arce","year":"2026","journal-title":"Reproduction"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-18881-2_9","article-title":"Prostasomes: Their Characterisation: Implications for Human Reproduction: Prostasomes and Human Reproduction","volume":"868","author":"Ronquist","year":"2015","journal-title":"Adv Exp Med Biol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1080\/03009734.2019.1592266","article-title":"Surface glycans contribute to differences between seminal prostasomes from normozoospermic and oligozoospermic men","volume":"124","author":"Milutinovi\u0107","year":"2019","journal-title":"Upsala J Med Sci"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12404","article-title":"Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches","volume":"13","author":"Welsh","year":"2024","journal-title":"J Extracell Vesicles"},{"key":"B50","doi-asserted-by":"publisher","first-page":"8822","DOI":"10.1038\/s41598-018-27180-z","article-title":"Extracellular vesicles with altered tetraspanin CD9 and CD151 levels confer increased prostate cell motility and invasion","volume":"8","author":"Brzozowski","year":"2018","journal-title":"Sci Rep"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.3390\/ani11051388","article-title":"Specific seminal plasma fractions are responsible for the modulation of sperm\u2013PMN binding in the donkey","volume":"11","author":"Mir\u00f3","year":"2021","journal-title":"Animals"},{"key":"B52","volume-title":"Salamons' Artificial Insemination of Sheep and Goats","author":"Evans","year":"1987"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.anireprosci.2025.107822","article-title":"The effect of freezing and thawing techniques on the in vitro quality of pellet-frozen ram semen","volume":"276","author":"Spanner","year":"2025","journal-title":"Anim Reprod Sci"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac194","article-title":"DAVID: a web server for functional enrichment analysis and functional annotation of gene lists, (2021 update)","volume":"50","author":"Sherman","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"B55","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang Da","year":"2009","journal-title":"Nat Protoc"},{"key":"B56","doi-asserted-by":"crossref","DOI":"10.1093\/biolre\/ioy032","article-title":"Binder of Sperm Proteins 1 and 5 have contrasting effects on the capacitation of ram spermatozoa","volume":"98","author":"Pini","year":"2018","journal-title":"Biol Reprod"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.105.045666","article-title":"Seminal DNase frees spermatozoa entangled in neutrophil extracellular traps","volume":"73","author":"Alghamdi","year":"2005","journal-title":"Biol Reprod"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.anireprosci.2008.10.015","article-title":"Species-specific interaction of seminal plasma on sperm-neutrophil binding","volume":"114","author":"Alghamdi","year":"2009","journal-title":"Anim Reprod Sci"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.theriogenology.2024.02.014","article-title":"The role of equine seminal plasma derived cysteine rich secretory protein 3 (CRISP3) in the interaction between polymorphonuclear neutrophils (PMNs) and populations of viable or dead spermatozoa, and bacteria","volume":"219","author":"Doty","year":"2024","journal-title":"Theriogenology"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2014.07.007","article-title":"Ram seminal plasma proteome and its impact on liquid preservation of spermatozoa","volume":"109","author":"Soleilhavoup","year":"2014","journal-title":"J Proteomics"},{"key":"B61","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.jprot.2013.05.029","article-title":"Proteomic characterization and cross species comparison of mammalian seminal plasma","volume":"91","author":"Druart","year":"2013","journal-title":"Proteomics"},{"key":"B62","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.anireprosci.2017.05.014","article-title":"Proteomic analysis of seminal plasma from locally-adapted \u201cCurraleiro P\u00e9-Duro bulls\u201d (Bos taurus): identifying biomarkers involved in sperm physiology in endangered animals for conservation of biodiversity","volume":"183","author":"Menezes","year":"2017","journal-title":"Anim Reprod Sci"},{"key":"B63","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.jprot.2016.04.026","article-title":"Characterization of the porcine seminal plasma proteome comparing ejaculate portions","volume":"142","author":"Perez-Patino","year":"2016","journal-title":"J Proteomics"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1530\/rep-25-0105","article-title":"Towards a kingdom of reproductive life - the core sperm proteome","volume":"169","author":"Pini","year":"2025","journal-title":"Reproduction"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2018.9485","article-title":"FKBP11 protects intestinal epithelial cells against inflammation-induced apoptosis via the JNK-caspase pathway in Crohn's disease","volume":"18","author":"Wang","year":"2018","journal-title":"Mol Med Rep"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2022.119305","article-title":"Nuclear Dishevelled: An enigmatic role in governing cell fate and Wnt signaling","volume":"1869","author":"Boligala","year":"2022","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202050600","article-title":"Nuclear Dishevelled targets gene regulatory regions and promotes tumor growth","volume":"22","author":"Castro-Piedras","year":"2021","journal-title":"EMBO Rep"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1126\/science.1149859","article-title":"Systemic leukocyte-directed siRNA delivery revealing Cyclin D1 as an anti-inflammatory target","volume":"319","author":"Peer","year":"2008","journal-title":"Science"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-020-02759-6","article-title":"Improvement of DC-based vaccines using adjuvant TLR4-binding 60S acidic ribosomal protein P2 and immune checkpoint inhibitors","volume":"70","author":"Jang","year":"2021","journal-title":"Cancer Immunol Immunother"},{"key":"B70","doi-asserted-by":"publisher","first-page":"68\u20131","DOI":"10.1095\/biolreprod.114.125740","article-title":"TLR4 signaling is a major mediator of the female tract response to seminal fluid in mice1","volume":"93","author":"Schjenken","year":"2015","journal-title":"Biol Reprod"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27956","article-title":"Na+\/H+ exchanger regulatory factor 1 knockout mice have an attenuated hepatic inflammatory response and are protected from cholestatic liver injury","volume":"62","author":"Li","year":"2015","journal-title":"Hepatology"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21207747","article-title":"Sodium hydrogen exchanger regulatory factor-1 (NHERF1) regulates fetal membrane inflammation","volume":"21","author":"Kammala","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B73","article-title":"PTTG1IP (PBF) is a prognostic marker and correlates with immune infiltrate in ovarian cancer","volume":"15","author":"Ma","year":"2023","journal-title":"Am J Transl Res"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90471-2","article-title":"An essential role for phosphatidylinositol transfer protein in phospholipase C-mediated inositol lipid signaling","volume":"74","author":"Thomas","year":"1993","journal-title":"Cell"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1083\/jcb1846oia15","article-title":"Critical role of phospholipase C\u03b32 in integrin and Fc receptor-mediated neutrophil functions and the effector phase of autoimmune arthritis","volume":"206","author":"Jakus","year":"2009","journal-title":"J Exp Med"},{"key":"B76","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1042\/bj3250299","article-title":"Co-operation of phosphatidylinositol transfer protein with phosphoinositide 3-kinase \u03b3 in the formylmethionyl-leucylphenylalanine-dependent production of phosphatidylinositol 3,4,5-trisphosphate in human neutrophils","volume":"325","author":"Kular","year":"1997","journal-title":"Biochem J"},{"key":"B77","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1093\/humupd\/dmi047","article-title":"Sperm transport in the female reproductive tract","volume":"12","author":"Suarez","year":"2005","journal-title":"Hum Reprod Update"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.3390\/ani13010052","article-title":"Binding of equine seminal lactoferrin\/superoxide dismutase (SOD-3) complex is biased towards dead spermatozoa","volume":"13","author":"Alghamdi","year":"2022","journal-title":"Animals"},{"key":"B79","first-page":"452","article-title":"Differential expression of complement regulatory proteins decay-accelerating factor (CD55), membrane cofactor protein (CD46) and CD59 during human spermatogenesis","volume":"81","author":"Simpson","year":"1994","journal-title":"Immunology"},{"key":"B80","article-title":"Potential role of bovine CD46 in the reproduction process","volume":"25","author":"Jankovicova","year":"2008","journal-title":"J Agrobiology"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.4149\/gpb_2011_si1_70","article-title":"Comparative fluorescence analysis of the bovine sperm using IVA-520 (anti-CD46 antibody) and lectins: probable localisation of CD46 on bovine sperm membrane","volume":"30","author":"Jankovicova","year":"2011","journal-title":"Gen Physiol Biophys"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.063495","article-title":"Factor H in porcine seminal plasma protects sperm against complement attack in genital tracts","volume":"285","author":"Sakaue","year":"2010","journal-title":"J Biol Chem"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.151.4.2159","article-title":"Clusterin, the human apolipoprotein and complement inhibitor, binds to complement C7, C8 beta, and the b domain of C9","volume":"151","author":"Tschopp","year":"1993","journal-title":"J Immunol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-010-1034-0","article-title":"The complement system","volume":"343","author":"Sarma","year":"2011","journal-title":"Cell Tissue Res"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.6b00530","article-title":"Proteomic investigation of ram spermatozoa and the proteins conferred by seminal plasma","volume":"15","author":"Pini","year":"2016","journal-title":"J Proteome Res"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2025.177901","article-title":"EDIL3 regulates pulmonary artery smooth muscle cell proliferation and migration via integrin \u03b1V\u03b23\/ERK1\/2 axis in pulmonary hypertension","author":"Gao","year":"2025","journal-title":"Eur J Pharmacol"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1126\/science.1165218","article-title":"Del-1, an endogenous leukocyte-endothelial adhesion inhibitor, limits inflammatory cell recruitment","volume":"322","author":"Choi","year":"2008","journal-title":"Science"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2260","article-title":"The leukocyte integrin antagonist Del-1 inhibits IL-17-mediated inflammatory bone loss","volume":"13","author":"Eskan","year":"2012","journal-title":"Nat Immunol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1159\/000485658","article-title":"Del-1 expression as a potential biomarker in triple-negative early breast cancer","volume":"94","author":"Lee","year":"2018","journal-title":"Oncology"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbo.2019.100238","article-title":"Tumor derived EDIL3 modulates the expansion and osteoclastogenesis of myeloid derived suppressor cells in murine breast cancer model","volume":"16","author":"Kun","year":"2019","journal-title":"J Bone Oncol"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00015-18","article-title":"Downregulation of microRNA eca-mir-128 in seminal exosomes and enhanced expression of CXCL16 in the stallion reproductive tract are associated with long-term persistence of equine arteritis virus","volume":"92","author":"Carossino","year":"2018","journal-title":"J Virol"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1016\/j.theriogenology.2023.09.026","article-title":"The effects of boar seminal plasma extracellular vesicles on sperm fertility","volume":"213","author":"Xu","year":"2024","journal-title":"Theriogenology"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2020.585276","article-title":"Expression pattern of seminal plasma extracellular vesicle small RNAs in boar semen","volume":"7","author":"Xu","year":"2020","journal-title":"Front Vet Sci"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1089\/bio.2024.0077","article-title":"Seminal plasma-derived exosome preserves the quality parameters of the post-thaw semen of bulls with low freezeability","volume":"23","author":"Shamsi","year":"2025","journal-title":"Biopreserv Biobank"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1080\/19396368.2021.1963012","article-title":"Production of bioactive recombinant ovine cysteine-rich secretory protein 1 in Escherichia coli","volume":"67","author":"Jorasia","year":"2021","journal-title":"Syst Biol Reprod Med"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1038\/aja.2010.77","article-title":"The role of cysteine-rich secretory proteins in male fertility","volume":"13","author":"Koppers","year":"2010","journal-title":"Asian J Androl"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0272.1998.tb01163.x","article-title":"Spermadhesins: a new protein family. Facts, hypotheses and perspectives","volume":"30","author":"T\u00f6pfer-Petersen","year":"1998","journal-title":"Andrologia"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1016\/s0014-5793(97)01514-7","article-title":"Biochemical and conformational characterisation of HSP-3, a stallion seminal plasma protein of the cysteine-rich secretory protein (CRISP) family","volume":"420","author":"Magdaleno","year":"1997","journal-title":"FEBS Lett"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.22500","article-title":"Sugar-coated sperm: Unraveling the functions of the mammalian sperm glycocalyx.","volume":"82","author":"Tecle","year":"2015","journal-title":"Mol Reprod Dev."},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.3109\/01485019108987656","article-title":"Loss of sperm surface sialic acid induces phagocytosis: an assay with a monoclonal antibody T21, which recognizes a 54K sialoglycoprotein","volume":"27","author":"Toshimori","year":"1991","journal-title":"Arch Androl"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2009.06.263","article-title":"Functional aspects of CD52 in reproduction","volume":"83","author":"Koyama","year":"2009","journal-title":"J Reprod Immunol"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwr087","article-title":"Letter to the glyco-forum: since there are PAMPs and DAMPs, there must be SAMPs? Glycan \u201cself-associated molecular patterns\u201d dampen innate immunity, but pathogens can mimic them","volume":"21","author":"Varki","year":"2011","journal-title":"Glycobiology"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.22500","article-title":"Sugar-coated sperm: Unraveling the functions of the mammalian sperm glycocalyx","volume":"82","author":"Tecle","year":"2015","journal-title":"Mol Reprod Dev"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1891264\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:15:39Z","timestamp":1788412539000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1891264\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":103,"alternative-id":["10.3389\/fimmu.2026.1891264"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1891264","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]},"article-number":"1891264"}}