{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T09:39:52Z","timestamp":1793353192230,"version":"4.5.0"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,8,22]],"date-time":"2016-08-22T00:00:00Z","timestamp":1471824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001779","name":"Monash University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001779","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2016,9]]},"abstract":"Abstract<\/jats:title>\n \n Despite antibiotic treatment, up to 40% of patients have impaired fertility after epididymitis due to serovars of\n Escherichia coli<\/jats:italic>\n , a frequent pathogen. The reasons for infertility are unclear, but it may result from epididymal duct obstruction. To determine whether\n E. coli<\/jats:italic>\n infection of the epididymis causes obstruction due to fibrosis, and to identify the key mediators, tissues from patients with epididymitis were assessed. Additionally, epididymitis was induced with uropathogenic\n E. coli<\/jats:italic>\n (\n UPEC<\/jats:styled-content>\n ) or commensal serovars in wild\u2010type and\n MyD88<\/jats:styled-content>\n \u2212\/\u2212<\/jats:sup>\n mice, which are relatively unresponsive to bacterial pathogens. Epididymal organ cultures were treated with activin A and bacteria and their histology and levels of cytokines and fibrosis markers were analysed. Patients with epididymitis showed severe fibrosis of the epididymal duct. In mice,\n UPEC<\/jats:styled-content>\n infection also caused fibrosis and ductal obstruction in the cauda epididymis. Levels of\n mRNA<\/jats:styled-content>\n for fibrotic markers (\u03b1\u2010smooth muscle actin, fibronectin) and cytokines (\n activin A<\/jats:italic>\n ,\n \n TNF\u03b1<\/jats:styled-content>\n <\/jats:italic>\n ,\n \n IL<\/jats:styled-content>\n \u20101\u03b1\n <\/jats:italic>\n ,\n \n IL<\/jats:styled-content>\n \u20101\u03b2\n <\/jats:italic>\n ,\n \n IL<\/jats:styled-content>\n \u20106\n <\/jats:italic>\n ) and total collagen levels were significantly elevated. This fibrotic response was blunted by the loss of\n MyD88<\/jats:styled-content>\n . Activin A induced fibrosis in cultured epididymis, which was inhibited by the activin\u2010binding protein follistatin. In summary, bacterial epididymitis causes fibrosis and obstruction. The milder tissue damage in\n Myd88<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n UPEC<\/jats:styled-content>\n epididymitis highlights the importance of the host response to infection in causing epididymal damage. Elevated levels of activin A\n in vivo<\/jats:italic>\n and fibrotic remodelling elicited by activin A\n in vitro<\/jats:italic>\n indicate that this cytokine is a potential target for supplementary treatment to antibiotic therapy. Copyright \u00a9 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.\n <\/jats:p>","DOI":"10.1002\/path.4748","type":"journal-article","created":{"date-parts":[[2016,5,24]],"date-time":"2016-05-24T16:36:14Z","timestamp":1464107774000},"page":"15-24","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["Uropathogenic\n Escherichia coli<\/i>\n causes fibrotic remodelling of the epididymis"],"prefix":"10.1002","volume":"240","author":[{"given":"Vera","family":"Michel","sequence":"first","affiliation":[{"name":"Institute of Anatomy and Cell Biology Justus\u2010Liebig\u2010University Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonggang","family":"Duan","sequence":"additional","affiliation":[{"name":"Centre of Reproductive Medicine and Andrology, First Affiliated Hospital of Shenzhen University Shenzhen Second People's Hospital People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Stoschek","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology Justus\u2010Liebig\u2010University Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudhanshu","family":"Bhushan","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology Justus\u2010Liebig\u2010University Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Middendorff","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology Justus\u2010Liebig\u2010University Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia M","family":"Young","sequence":"additional","affiliation":[{"name":"Hudson Institute of Medical Research Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate L","family":"Loveland","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Sciences Monash University Melbourne Victoria Australia"},{"name":"Department of Anatomy and Developmental Biology Monash University Melbourne Victoria Australia"},{"name":"Department of Biochemistry and Molecular Biology Monash University Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M De","family":"Kretser","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Developmental Biology Monash University Melbourne Victoria Australia"},{"name":"Hudson Institute of Medical Research Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark P","family":"Hedger","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Developmental Biology Monash University Melbourne Victoria Australia"},{"name":"Hudson Institute of Medical Research Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Meinhardt","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology Justus\u2010Liebig\u2010University Giessen Germany"},{"name":"Department of Molecular and Translational Sciences Monash University Melbourne Victoria Australia"},{"name":"Hudson Institute of Medical Research Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,8,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3399\/bjgp10X532413"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2014.12.005"},{"key":"e_1_2_7_4_1","article-title":"EAU Guidelines Office: Arnhem","author":"EAU Guidelines. 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