{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T03:46:43Z","timestamp":1783741603110,"version":"3.55.0"},"reference-count":60,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,1,29]],"date-time":"2016-01-29T00:00:00Z","timestamp":1454025600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/CVT\/105022\/2008"],"award-info":[{"award-number":["PTDC\/CVT\/105022\/2008"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/64416\/2009"],"award-info":[{"award-number":["SFRH\/BD\/64416\/2009"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/CVT\/105022\/2008"],"award-info":[{"award-number":["PTDC\/CVT\/105022\/2008"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BPD\/47079\/2008"],"award-info":[{"award-number":["SFRH\/BPD\/47079\/2008"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Spermatozoa undergo sequential maturation changes during their transit along the epididymis. These changes are modulated by the epididymal epithelium and require a finely tuned gene expression. The Notch cell signaling pathway is a major regulator of cell fate decisions in several tissues, including the testis. Here, we evaluated the transcription and expression patterns of Notch components (<jats:italic>Notch1\u20103<\/jats:italic>,<jats:italic>Dll1<\/jats:italic>,<jats:italic>Dll4,<\/jats:italic>and<jats:italic>Jagged1<\/jats:italic>) and effectors (<jats:italic>Hes1\u20102<\/jats:italic>and<jats:italic>Hes5<\/jats:italic>) in the adult mouse epididymis, and evaluated the role of Notch signaling in the epididymis through its in\u00a0vivo blockade following administration of an inhibitor (<jats:styled-content style=\"fixed-case\">DAPT<\/jats:styled-content>). Notch components and effectors were dynamically transcribed and expressed in the epididymis and<jats:italic>vas deferens<\/jats:italic>, each segment exhibiting a specific combination of epithelial receptor\/ligand\/effector expression patterns. Nuclear detection of Notch effectors indicates that Notch signaling was active. Notch components (but not effectors) were identified in the cytoplasmic droplet of spermatozoa, in a dynamic and specific pattern along the epididymis. In addition, Notch components were identified within large and small vesicles in the epididymal lumen. A purified population of these membranous vesicles from different epididymal segments was obtained, and through dot blot analysis, it was confirmed that Notch components were carried within these vesicles in a dynamic pattern along the epididymal lumen. We hypothesize that these vesicles (epididymosomes) allow Notch signaling at distance from epididymal epithelial cells to spermatozoa.<jats:styled-content style=\"fixed-case\">DAPT<\/jats:styled-content>\u2010induced in\u00a0vivo Notch signaling blockade, although showing a low efficiency, disrupted the expression patterns of Notch components and effectors in the epididymal epithelium and in spermatozoa, and significantly decreased sperm motility, although not affecting male fertility. These results prompt for a regulatory role of Notch signaling in epididymal epithelial function and sperm maturation.<\/jats:p>","DOI":"10.1111\/andr.12144","type":"journal-article","created":{"date-parts":[[2016,1,30]],"date-time":"2016-01-30T01:07:19Z","timestamp":1454116039000},"page":"314-327","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Notch signaling in the epididymal epithelium regulates sperm motility and is transferred at a distance within epididymosomes"],"prefix":"10.1111","volume":"4","author":[{"given":"D.","family":"Murta","sequence":"first","affiliation":[{"name":"Reproduction and Development CIISA Faculty of Veterinary Medicine University of Lisbon Lisbon Portugal"},{"name":"CBIOS \u2010 Research Centre for Biosciences and Health Technologies Faculty of Veterinary Medicine Lus\u00f3fona University of Humanities and Technologies Lisboa Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Batista","sequence":"additional","affiliation":[{"name":"Reproduction and Development CIISA Faculty of Veterinary Medicine University of Lisbon Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Silva","sequence":"additional","affiliation":[{"name":"Reproduction and Development CIISA Faculty of Veterinary Medicine University of Lisbon Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Trindade","sequence":"additional","affiliation":[{"name":"Reproduction and Development CIISA Faculty of Veterinary Medicine University of Lisbon Lisbon Portugal"},{"name":"Gulbenkian Institute of Science Oeiras Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Henrique","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine Faculty of Medicine University of Lisbon Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Duarte","sequence":"additional","affiliation":[{"name":"Reproduction and Development CIISA Faculty of Veterinary Medicine University of Lisbon Lisbon Portugal"},{"name":"Gulbenkian Institute of Science Oeiras Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Lopes\u2010da\u2010Costa","sequence":"additional","affiliation":[{"name":"Reproduction and Development CIISA Faculty of Veterinary Medicine University of Lisbon Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,1,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1092090207"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","DOI":"10.1002\/j.1939-4640.1996.tb01776.x","article-title":"Apical and narrow cells are distinct cell types differing in their structure, distribution, and functions in the adult rat epididymis","volume":"17","author":"Adamali HI","year":"1996","journal-title":"J Androl"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7716513"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-012-1381-0"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43025"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-009-8668-7"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2012.00081"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0065364"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02773"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200409205"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-012-9300-2"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)37153-9"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0710427"},{"key":"e_1_2_8_15_1","first-page":"1085","article-title":"Relations between the fertilizing ability and metabolism of epididymal spermatozoa","volume":"20","author":"Dacheux JL","year":"1980","journal-title":"Reprod Fertil Dev"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.161102498"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.052043"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm477"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.1013"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.20170"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.106.054692"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.2164\/jandrol.05108"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.2011.01203.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.2164\/jandrol.111.013086"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa003005"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-08-0207"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.2004.tb02843.x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001830202"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.110.088708"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1076695"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1071\/RD9960553"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.110.087353"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.1080340104"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2795(199902)52:2<225::AID-MRD14>3.0.CO;2-M"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.12.021"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2006.09.010"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072767"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0113365"},{"key":"e_1_2_8_39_1","first-page":"161","volume-title":"Manipulating the Mouse Embryo","author":"Nagy A","year":"2003"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.8.2196"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2012.01.066"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.105.049304"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.2003.tb02653.x"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2009.05.566"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-08-239228"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2002.6528"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.10.020"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2009.10.004"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2012.07.003"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-08-174508"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2005.03.005"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7262.2007.00281.x"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001540104"},{"key":"e_1_2_8_54_1","doi-asserted-by":"crossref","first-page":"451","DOI":"10.5858\/2009-0665-OA.1","article-title":"Differential Notch1 and Notch2 expression and frequent activation of Notch signaling in gastric cancers","volume":"135","author":"Sun Y","year":"2011","journal-title":"Arch Pathol Lab Med"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2008-0580"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-05-087353"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.1995.tb00532.x"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1530\/rep.0.1250871"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.403287"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600069"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10238-012-0203-8"}],"container-title":["Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fandr.12144","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fandr.12144","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/api.wiley.com\/onlinelibrary\/chorus\/v1\/articles\/10.1111%2Fandr.12144","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.12144","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T02:05:27Z","timestamp":1718330727000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/andr.12144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1,29]]},"references-count":60,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,3]]}},"alternative-id":["10.1111\/andr.12144"],"URL":"https:\/\/doi.org\/10.1111\/andr.12144","archive":["Portico"],"relation":{},"ISSN":["2047-2919","2047-2927"],"issn-type":[{"value":"2047-2919","type":"print"},{"value":"2047-2927","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1,29]]},"assertion":[{"value":"2014-05-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-11-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}