{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T22:17:16Z","timestamp":1789856236194,"version":"4.0.1"},"reference-count":87,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T00:00:00Z","timestamp":1563494400000},"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"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The interface between the epididymis and the immune system is implicated in many male reproductive pathologies. The resident immune cell populations and immune\u2010environment within the epididymis are significantly different from the testis, which is an immune\u2010privileged site. Moreover, the immune cell subsets and immunological responses between different regions of the epididymis vary considerably. The cauda epididymis is more susceptible to autoimmune responses than the caput in rodent models of active immunization or suppressed immune tolerance, and in men with congenital or physical damage to the reproductive tract. Activins are members of the transforming growth factor\u2010\u03b2 family of cytokines that are crucial for testis and epididymal development; however, they also have complex immunoregulatory properties and may play an essential role in the regulation of immunity in the reproductive tract.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Our recent research and relevant publications by other researchers identified following a PubMed search are reviewed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The caput epididymis displays elevated endogenous expression of activins A and B and the immunoregulatory gene, indoleamine\u20102,3\u2010dioxygenase, co\u2010existing with an extensive population of intra\u2010epithelial and interstitial macrophages and dendritic cells, which appear to be involved in regulating tolerance against sperm antigens. The caput is also relatively resistant to inflammatory damage caused by autoimmunity or bacterial infection, but the cauda, which exhibits low activin expression and high levels of the activin\u2010binding protein, follistatin, is highly susceptible to inflammatory damage. Paradoxically, inflammation in the cauda induces increased activin production, and inhibition of activin activity reduces inflammatory responses. Studies using mouse models with altered levels of activins and follistatin indicate a relationship between the activins and genes involved in inflammation and immunoregulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The existing data indicate that activins play a complex role in controlling inflammation and immunity in the epididymis and vas deferens.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.12682","type":"journal-article","created":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T10:31:05Z","timestamp":1563532265000},"page":"703-711","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Activins, follistatin and immunoregulation in the epididymis"],"prefix":"10.1111","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5584-1371","authenticated-orcid":false,"given":"R.","family":"Wijayarathna","sequence":"first","affiliation":[{"name":"Centre for Reproductive Health Hudson Institute of Medical Research Clayton Vic. Australia"},{"name":"Department of Molecular and Translational Sciences School of Clinical Sciences Monash University Clayton Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. P.","family":"Hedger","sequence":"additional","affiliation":[{"name":"Centre for Reproductive Health Hudson Institute of Medical Research Clayton Vic. Australia"},{"name":"Department of Molecular and Translational Sciences School of Clinical Sciences Monash University Clayton Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,19]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000318107"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jez.1401630310"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.1999.tb02531.x"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-005-0151-7"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/78161"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2088"},{"key":"e_1_2_13_8_1","first-page":"723","article-title":"Immunoregulation by members of the TGF\u03b2 superfamily","volume":"16","author":"Chen W","year":"2016","journal-title":"Nat Rev"},{"key":"e_1_2_13_9_1","first-page":"157","article-title":"The male infertility office visit","volume":"67","author":"Dadhich P","year":"2015","journal-title":"Minerva Urol Nefrol"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004410051177"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/and.12463"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmy009"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0185(199707)248:3<380::AID-AR11>3.0.CO;2-L"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.4161\/21565562.2014.979619"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0034-1375184"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/2051-4190-23-8"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.21.13835"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-198310000-00014"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.2164\/jandrol.111.012989"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-397175-3.00019-3"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2013.03.003"},{"key":"e_1_2_13_22_1","first-page":"255","volume-title":"Vitam Horm","author":"Hedger MP","year":"2011"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.06862"},{"key":"e_1_2_13_24_1","first-page":"5","article-title":"Disease spectrum and treatment patterns in a local male infertility clinic","volume":"21","author":"Ho KL","year":"2015","journal-title":"Hong Kong Med J"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1071\/RD13372"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0802124"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-129-2-815"},{"key":"e_1_2_13_28_1","first-page":"170","article-title":"Establishment of an experimental model of autoimmune epididymo\u2010orchitis induced by the transfer of a T\u2010cell line in mice","volume":"15","author":"Itoh M","year":"1992","journal-title":"Int J Androl"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/6.12.1107"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705971104"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.172114"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066494"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2014.02.011"},{"key":"e_1_2_13_34_1","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.4049\/jimmunol.130.6.2675","article-title":"Immunopathology of murine experimental allergic orchitis","volume":"130","author":"Kohno S","year":"1983","journal-title":"J Immunol"},{"key":"e_1_2_13_35_1","first-page":"271","article-title":"The role of the epididymis in human infertility","volume":"53","author":"Kretser D","year":"1998","journal-title":"J Reprod Fertil"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.10.009"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M700737200"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1530\/rep.1.01072"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.21.7217"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006254-198702000-00015"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dey235"},{"key":"e_1_2_13_42_1","first-page":"173","article-title":"Localization of immunocompetent cells in the human epididymis","volume":"39","author":"Marchlewicz M","year":"2001","journal-title":"Folia Histochem Cytobiol"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(86)91021-1"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90549-E"},{"key":"e_1_2_13_45_1","first-page":"37","article-title":"Identification and analysis of tumor suppressor genes using transgenic mouse models","volume":"5","author":"Matzuk MM","year":"1994","journal-title":"Semin Cancer Biol"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/360313a0"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/374356a0"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/374360a0"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2010.03.022"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.110.086231"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4748"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.109.079855"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31178"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)42014-5"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.1989.tb01289.x"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.06706"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2077"},{"key":"e_1_2_13_58_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01882"},{"key":"e_1_2_13_59_1","doi-asserted-by":"publisher","DOI":"10.1071\/ZO9570223"},{"key":"e_1_2_13_60_1","doi-asserted-by":"publisher","DOI":"10.4103\/1008-682X.168791"},{"key":"e_1_2_13_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012515400-0\/50027-0"},{"key":"e_1_2_13_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(87)90430-X"},{"key":"e_1_2_13_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0272.2008.00837.x"},{"key":"e_1_2_13_64_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod61.3.705"},{"key":"e_1_2_13_65_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-10-0493"},{"key":"e_1_2_13_66_1","doi-asserted-by":"publisher","DOI":"10.1163\/156856003322315604"},{"key":"e_1_2_13_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)82296-7"},{"key":"e_1_2_13_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.1982.tb00277.x"},{"key":"e_1_2_13_69_1","doi-asserted-by":"publisher","DOI":"10.5604\/12321966.1203881"},{"key":"e_1_2_13_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2004.02.007"},{"key":"e_1_2_13_71_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703445104"},{"key":"e_1_2_13_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2004.03.009"},{"key":"e_1_2_13_73_1","first-page":"293","article-title":"Murine autoimmune oophoritis, epididymoorchitis, and gastritis induced by day 3 thymectomy. Immunopathology","volume":"126","author":"Tung K","year":"1987","journal-title":"Am J Pathol"},{"key":"e_1_2_13_74_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.23.8282"},{"key":"e_1_2_13_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/321776a0"},{"key":"e_1_2_13_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2018.01.003"},{"key":"e_1_2_13_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.06.030"},{"key":"e_1_2_13_78_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmv058"},{"key":"e_1_2_13_79_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12337"},{"key":"e_1_2_13_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2017.10.013"},{"key":"e_1_2_13_81_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-17-0485"},{"key":"e_1_2_13_82_1","doi-asserted-by":"publisher","DOI":"10.1071\/RD11287"},{"key":"e_1_2_13_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ucl.2013.08.006"},{"key":"e_1_2_13_84_1","doi-asserted-by":"publisher","DOI":"10.1038\/370341a0"},{"key":"e_1_2_13_85_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00478.2011"},{"key":"e_1_2_13_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2012.09.018"},{"key":"e_1_2_13_87_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.110.090324"},{"key":"e_1_2_13_88_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.5.2516"}],"container-title":["Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fandr.12682","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.12682","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/andr.12682","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.12682","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T07:20:21Z","timestamp":1694330421000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/andr.12682"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,19]]},"references-count":87,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,9]]}},"alternative-id":["10.1111\/andr.12682"],"URL":"https:\/\/doi.org\/10.1111\/andr.12682","archive":["Portico"],"relation":{},"ISSN":["2047-2919","2047-2927"],"issn-type":[{"value":"2047-2919","type":"print"},{"value":"2047-2927","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,19]]},"assertion":[{"value":"2019-05-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}