{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:21:03Z","timestamp":1792632063342,"version":"4.5.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T00:00:00Z","timestamp":1602201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["#2015\/08227-0"],"award-info":[{"award-number":["#2015\/08227-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["#2017\/20102-3"],"award-info":[{"award-number":["#2017\/20102-3"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Whey-acidic protein four-disulfide core domain (WFDC) genes display putative roles in innate immunity and fertility. In mice, a locus on chromosome 2 contains 5 and 11 Wfdc genes in its centromeric and telomeric subloci, respectively. Although Wfdc genes are highly expressed in the epididymis, their contributions to epididymal function remain elusive. Here, we investigated whether Wfdc genes are regulated in response to lipopolysaccharide (LPS)-induced epididymitis, an inflammatory condition that impairs male fertility. We induced epididymitis in mice via (i) interstitial LPS injection into epididymal initial segment and (ii) intravasal LPS injection into the vas deferens towards cauda epididymis. Interstitial and intravasal LPS induced a differential upregulation of inflammatory mediators (interleukin 1 beta, interleukin 6, tumor necrosis factor, interferon gamma, and interleukin 10) in the initial segment and cauda epididymis within 72\u00a0h post-treatment. These changes were accompanied by a time-dependent endotoxin clearance from the epididymis. In the initial segment, interstitial LPS upregulated all centromeric (Slpi, Wfdc5, Wfdc12, Wfdc15a, and Wfdc15b) and five telomeric (Wfdc2, Wfdc3, Wfdc6b, Wfdc10, and Wfdc13) Wfdc transcripts at 24 and 72\u00a0h. In the cauda epididymis, intravasal LPS upregulated Wfdc5 and Wfdc2 transcripts at 24\u00a0h, followed by a downregulation of Wfdc15b and three telomeric (Wfdc6a, Wfdc11, and Wfdc16) gene transcripts at 72\u00a0h. Pharmacological inhibition of nuclear factor kappa B activation prevented LPS-induced upregulation of centromeric and telomeric Wfdc genes depending on the epididymal region. We show that LPS-induced inflammation differentially regulated the Wfdc locus in the proximal and distal epididymis, indicating region-specific roles for the Wfdc family in innate immune responses during epididymitis.<\/jats:p>","DOI":"10.1093\/biolre\/ioaa189","type":"journal-article","created":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T08:55:07Z","timestamp":1602233707000},"page":"144-158","source":"Crossref","is-referenced-by-count":22,"title":["Lipopolysaccharide-induced epididymitis modifies the transcriptional profile of\n                    <i>Wfdc<\/i>\n                    genes in mice"],"prefix":"10.1093","volume":"104","author":[{"given":"Alexandre D","family":"Andrade","sequence":"first","affiliation":[{"name":"Department of Biophysics and Pharmacology , , Universidade Estadual Paulista \u201cJ\u00falio de Mesquita Filho\u201d, Botucatu, SP,","place":["Brazil"]},{"name":"Instituto de Bioci\u00eancias de Botucatu , , Universidade Estadual Paulista \u201cJ\u00falio de Mesquita Filho\u201d, Botucatu, SP,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscila G C","family":"Almeida","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Pharmacology , , Universidade Estadual Paulista \u201cJ\u00falio de Mesquita Filho\u201d, Botucatu, SP,","place":["Brazil"]},{"name":"Instituto de Bioci\u00eancias de Botucatu , , Universidade Estadual Paulista \u201cJ\u00falio de Mesquita Filho\u201d, Botucatu, SP,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noemia A P","family":"Mariani","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Pharmacology , , Universidade Estadual Paulista \u201cJ\u00falio de Mesquita Filho\u201d, Botucatu, SP,","place":["Brazil"]},{"name":"Instituto de Bioci\u00eancias de Botucatu , , Universidade Estadual Paulista \u201cJ\u00falio de Mesquita Filho\u201d, Botucatu, SP,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geanne A","family":"Freitas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology , , Escola Paulista de Medicina, S\u00e3o Paulo, SP,","place":["Brazil"]},{"name":"Universidade Federal de S\u00e3o Paulo , , Escola Paulista de Medicina, S\u00e3o Paulo, SP,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9lio","family":"Kushima","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Pharmacology , , Universidade Estadual Paulista \u201cJ\u00falio de Mesquita Filho\u201d, Botucatu, SP,","place":["Brazil"]},{"name":"Instituto de Bioci\u00eancias de Botucatu , , Universidade Estadual Paulista \u201cJ\u00falio de Mesquita Filho\u201d, Botucatu, SP,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 L","family":"Filadelpho","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology , , Universidade Estadual Paulista \u201cJ\u00falio de Mesquita Filho\u201d, Botucatu, SP,","place":["Brazil"]},{"name":"Instituto de Bioci\u00eancias de Botucatu , , Universidade Estadual Paulista \u201cJ\u00falio de Mesquita Filho\u201d, Botucatu, SP,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Ang\u00e9lica","family":"Spadella","sequence":"additional","affiliation":[{"name":"Discipline of Human Embryology , , Mar\u00edlia, SP,","place":["Brazil"]},{"name":"Faculdade de Medicina de Mar\u00edlia , , Mar\u00edlia, SP,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Christina W","family":"Avellar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology , , Escola Paulista de Medicina, S\u00e3o Paulo, SP,","place":["Brazil"]},{"name":"Universidade Federal de S\u00e3o Paulo , , Escola Paulista de Medicina, S\u00e3o Paulo, SP,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erick J R","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Pharmacology , , Universidade Estadual Paulista \u201cJ\u00falio de Mesquita Filho\u201d, Botucatu, SP,","place":["Brazil"]},{"name":"Instituto de Bioci\u00eancias de Botucatu , , Universidade Estadual Paulista \u201cJ\u00falio de Mesquita Filho\u201d, Botucatu, SP,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,10,9]]},"reference":[{"key":"2026041420171331600_ref1","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.eururo.2014.12.005","article-title":"Acute epididymitis revisited: impact of molecular diagnostics on etiology and contemporary guideline recommendations","volume":"68","author":"Pilatz","year":"2015","journal-title":"Eur 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