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Inflammation is triggered by alert molecules released following tissue stress or injury. These include uracil\u2010diphosphate glucose (UDP)\u2010glucose, which activates the pro\u2010inflammatory P2Y14 receptor (P2Y14), and induces immune cell recruitment. However, little is known about P2Y14 in the epididymis and its potential activation following vasectomy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>(i) To localize P2Y14 in the human excurrent duct; and (ii) to examine the effect of vasectomy on P2Y14 protein and <jats:italic>P2RY14<\/jats:italic> mRNA content, the production of selected cytokines and chemokines, and immune cell recruitment in the epididymis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and methods<\/jats:title><jats:p>In situ hybridization, qRT\u2010PCR, western blotting, immunohistochemistry, and immunofluorescence were performed in banked human epididymis samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>P2RY14<\/jats:italic> mRNA and P2Y14 protein were detected in epithelial cells in the efferent duct, epididymis and vas deferens in non\u2010vasectomized men. Keratin 5 (KRT5)\u2010positive basal cells were strongly labeled for P2Y14 in all epididymal segments. A progressive apical localization was detected in principal cells (negative for the proton pump V\u2010ATPase) from the <jats:italic>corpus<\/jats:italic> to the <jats:italic>cauda<\/jats:italic>. A subset of V\u2010ATPase\u2010positive clear cells also showed strong P2Y14 labeling. Vasectomy induced an increase in <jats:italic>P2RY14<\/jats:italic> mRNA in the <jats:italic>corpus<\/jats:italic> and <jats:italic>cauda<\/jats:italic>, and stronger apical labeling in principal cells in the <jats:italic>corpus<\/jats:italic>. <jats:italic>CXCL10<\/jats:italic> mRNA increased in the <jats:italic>cauda<\/jats:italic> and <jats:italic>CCL2<\/jats:italic> mRNA decreased in the <jats:italic>corpus<\/jats:italic> of vasectomized versus non\u2010vasectomized men. No change in <jats:italic>IL\u20108<\/jats:italic> and <jats:italic>IL\u20101\u03b2<\/jats:italic> mRNA was detected. Numerous CD45<jats:sup>+<\/jats:sup> leukocytes were detected in the interstitium of the <jats:italic>corpus<\/jats:italic> and <jats:italic>cauda<\/jats:italic> following vasectomy, while only a few were seen in non\u2010vasectomized men. Several CD45<jats:sup>+<\/jats:sup> leukocytes, some of which containing spermatozoa, were detected in the <jats:italic>corpus<\/jats:italic> lumen following vasectomy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion and conclusion<\/jats:title><jats:p>Our study indicates that vasectomy\u2010induced spermatozoa congestion may lead to an inflamed\u2010prone local environment characterized by potential activation of P2Y14 and recruitment of immune cells in the epididymis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.13284","type":"journal-article","created":{"date-parts":[[2022,8,27]],"date-time":"2022-08-27T12:20:40Z","timestamp":1661602840000},"page":"1522-1539","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Expression of the pro\u2010inflammatory P2Y14 receptor in the non\u2010vasectomized and vasectomized human epididymis"],"prefix":"10.1111","volume":"10","author":[{"given":"Larissa Berloffa","family":"Belardin","sequence":"first","affiliation":[{"name":"Centre Hospitalier Universitaire de Qu\u00e9bec\u2014Research Centre, Department of Obstetrics, Gynecology and Reproduction, and Centre de Recherche en Reproduction, D\u00e9veloppement et Sant\u00e9 Interg\u00e9n\u00e9rationnelle, Faculty of Medicine Universit\u00e9 Laval  Qu\u00e9bec Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"L\u00e9gar\u00e9","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Qu\u00e9bec\u2014Research Centre, Department of Obstetrics, Gynecology and Reproduction, and Centre de Recherche en Reproduction, D\u00e9veloppement et Sant\u00e9 Interg\u00e9n\u00e9rationnelle, Faculty of Medicine Universit\u00e9 Laval  Qu\u00e9bec Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Qu\u00e9bec\u2014Research Centre, Department of Obstetrics, Gynecology and Reproduction, and Centre de Recherche en Reproduction, D\u00e9veloppement et Sant\u00e9 Interg\u00e9n\u00e9rationnelle, Faculty of Medicine Universit\u00e9 Laval  Qu\u00e9bec Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9284-9420","authenticated-orcid":false,"given":"Cl\u00e9mence","family":"Belleann\u00e9e","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Qu\u00e9bec\u2014Research Centre, Department of Obstetrics, Gynecology and Reproduction, and Centre de Recherche en Reproduction, D\u00e9veloppement et Sant\u00e9 Interg\u00e9n\u00e9rationnelle, Faculty of Medicine Universit\u00e9 Laval  Qu\u00e9bec Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Breton","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de 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