{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T03:54:33Z","timestamp":1785297273298,"version":"3.55.0"},"reference-count":33,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2016,5,11]],"date-time":"2016-05-11T00:00:00Z","timestamp":1462924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81100463"],"award-info":[{"award-number":["81100463"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31301009"],"award-info":[{"award-number":["31301009"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Science &amp; Technology Pillar Program during the 12th Five-year Plan Period","award":["2012BAI31B08"],"award-info":[{"award-number":["2012BAI31B08"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Background: Spermatozoa become mature and acquire fertilizing capacity during their passage through the epididymal lumen. In this study, we identified new epididymal luminal fluid proteins involved in sperm maturation in infertile rats by dutasteride, a dual 5\u03b1-reductase inhibitor, in order to provide potential epididymal targets for new contraceptives and infertility treatment. Methods: Male rats were treated with dutasteride for 28 consecutive days. We observed the protein expression profiles in the epididymal luminal fluids in infertile and normal rats using isobaric tags for relative and absolute quantitation (iTRAQ) technique. The confidence of proteome data was validated by enzyme-linked immunosorbent assays. Results: 1045 proteins were tested, and 23 of them presented different expression profiling in the infertile and normal rats. The seven proteins were down-regulated, and 16 proteins were up-regulated. Among the seven proteins which were significantly down-regulated by dutasteride in the epididymal luminal fluids, there were three \u03b2-defensins (Defb2, Defb18 and Defb39), which maybe the key proteins involved in epididymal sperm maturation and male fertility. Conclusions: We report for the first time that dutasteride influences the protein expression profiling in the epididymal luminal fluids of rats, and this result provides some new epididymal targets for male contraception and infertility therapy.<\/jats:p>","DOI":"10.3390\/molecules21050602","type":"journal-article","created":{"date-parts":[[2016,5,11]],"date-time":"2016-05-11T10:53:59Z","timestamp":1462964039000},"page":"602","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Identification of New Epididymal Luminal Fluid Proteins Involved in Sperm Maturation in Infertile Rats Treated by Dutasteride Using iTRAQ"],"prefix":"10.3390","volume":"21","author":[{"given":"Shu-Wu","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Reproductive Pharmacology, Key Lab of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-Ting","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Reproductive Pharmacology, Key Lab of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Juan","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Shanghai Eighth People\u2019s Hospital, Shanghai 200233, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Cao","sequence":"additional","affiliation":[{"name":"Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai 200437, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"Ming Qi Natural Healthcare Center, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie-Yun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Reproductive Pharmacology, Key Lab of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Hua","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Reproductive Pharmacology, Key Lab of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Jie","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Reproductive Pharmacology, Key Lab of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Reproductive Pharmacology, Key Lab of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/216816a0","article-title":"Sperm maturation in rabbit epididymis","volume":"216","year":"1967","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Choi, H., Han, C., Jin, S., Kwon, J.T., Kim, J., Jeong, J., Kim, J., Ham, S., Jeon, S., and Yoo, Y.J. (2015). Reduced fertility and altered epididymal and sperm integrity in mice lacking ADAM7. Biol. Reprod., 93.","DOI":"10.1095\/biolreprod.115.130252"},{"key":"ref_3","first-page":"2725","article-title":"Luminal fluid of epididymis and vas deferens contributes to sperm chromatin fragmentation","volume":"30","author":"Gawecka","year":"2015","journal-title":"Hum. Reprod."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1016\/j.cell.2015.10.029","article-title":"Post-transcriptional Wnt Signaling Governs Epididymal Sperm Maturation","volume":"163","author":"Koch","year":"2015","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/ncb1127","article-title":"An epididymis-specific \u03b2-defensin is important for the initiation of sperm maturation","volume":"6","author":"Zhou","year":"2004","journal-title":"Nat. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Mandon, M., and Cyr, D.G. (2015). Tricellulin and its role in the epididymal epithelium of the rat. Biol. Reprod., 92.","DOI":"10.1095\/biolreprod.114.120824"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1111\/j.2047-2927.2014.00251.x","article-title":"Mononuclear phagocytes rapidly clear apoptotic epithelial cells in the proximal epididymis","volume":"2","author":"Smith","year":"2014","journal-title":"Andrology"},{"key":"ref_8","first-page":"237","article-title":"Blood-tissue barriers: Morphofunctional and immunological aspects of the blood-testis and blood-epididymal barriers","volume":"763","author":"Auharek","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hu, S.G., Zou, M., Yao, G.X., Ma, W.B., Zhu, Q.L., Li, X.Q., Chen, Z.J., and Sun, Y. (2014). Androgenic regulation of \u03b2-defensins in the mouse epididymis. Reprod. Biol. Endocrinol., 12.","DOI":"10.1186\/1477-7827-12-76"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"592","DOI":"10.2164\/jandrol.111.014266","article-title":"Androgen action in the epididymis","volume":"32","author":"Robaire","year":"2011","journal-title":"J. Androl."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4504","DOI":"10.1210\/en.2010-0023","article-title":"Identification of early response genes and pathway activated by androgens in the initial segment and caput regions of the regressed rat epididymis","volume":"151","author":"Hamzeh","year":"2010","journal-title":"Endocrinology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4797","DOI":"10.1007\/s11033-011-1271-7","article-title":"Effect of surgical castration on expression of TRPM8 in urogenital tract of male rats","volume":"39","author":"Yang","year":"2012","journal-title":"Mol. Biol. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0960-0760(97)00158-1","article-title":"PNU 157706, a novel dual type I and II5\u03b1-reductase inhibitor","volume":"64","author":"Giudici","year":"1998","journal-title":"J. Steroid. Biochem. Mol. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1095\/biolreprod.104.033548","article-title":"Effects of PNU157706, a dual 5\u03b1-reductase inhibitor, on rat epididymal sperm maturation and fertility","volume":"72","author":"Henderson","year":"2005","journal-title":"Biol. Reprod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/1477-7827-11-59","article-title":"Sperm-associated antigen11A is expressed exclusively in the principal cells of the mouse caput epididymis in an androgen-dependent manner","volume":"11","author":"Pujianto","year":"2013","journal-title":"Reprod. Biol. Endocrinol"},{"key":"ref_16","first-page":"17","article-title":"Inhibitory effect of dutasteride on the expressions of epididymal Claudin1 and \u03b2-catenin in male rats","volume":"21","author":"Xie","year":"2015","journal-title":"Zhonghua Nan Ke Xue"},{"key":"ref_17","unstructured":"Liu, X., Jin, S.H., Liu, X.X., Wang, W.J., and Liu, F.J. (2014). Proteome profiling of the sperm maturation milieu in the rhesus monkey (Macaca mulatta) epididymis. Reprod. Fertil. Dev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1071\/RD09091","article-title":"New proteins identified in epididymal fluid from the platypus (Ornithorhynchus anatinus)","volume":"21","author":"Dacheux","year":"2009","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zhou, Y.S., Webb, S., Lettice, L., Tardif, S., Kilanowski, F., Tyrrell, C., Macpherson, H., Semple, F., Tennant, P., and Baker, T. (2013). Partial deletion of chromosome 8 \u03b2-defensin cluster confers sperm dysfunction and infertility in male mice. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003826"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12270","DOI":"10.1074\/jbc.M112.411884","article-title":"The novel human \u03b2-defensin 114 regulates lipopolysaccharide (LPS)-mediated inflammation and protects sperm from motility loss","volume":"288","author":"Yu","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Seachrist, D.D., Johnson, E., Magee, C., Clay, C.M., Graham, J.K., and Veeramachaneni, D.N. (2012). Keri RA. Overexpression of follistatin in the mouse epididymis disrupts fluid resorption and sperm transit in testicular excurrent ducts. Biol. Reprod., 87.","DOI":"10.1095\/biolreprod.111.097527"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.mce.2015.01.013","article-title":"Dynamic changes in the spatio-temporal expression of the \u03b2-defensin SPAG11C in the developing rat epididymis and its regulation by androgens","volume":"404","author":"Ribeiro","year":"2015","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1007\/s00438-014-0854-0","article-title":"Transcriptional regulation of the rat sperm-associated antigen 11e (Spag 11e) gene during endotoxin challenge","volume":"289","author":"Biswas","year":"2014","journal-title":"Mol. Genet. Genomics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1093\/molehr\/gau050","article-title":"Importance of \u03b2-defensins in sperm function","volume":"20","author":"Dorin","year":"2014","journal-title":"Mol. Hum. Reprod."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1071\/RD13153","article-title":"Novel subclass of bovine \u03b2-defensins links reproduction and immunology","volume":"26","author":"Narciandi","year":"2014","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1093\/humrep\/det237","article-title":"Epididymal specific, selenium-independent GPX5 protects cells from oxidative stress-induced lipid peroxidation and DNA mutation","volume":"28","author":"Robson","year":"2013","journal-title":"Hum. Reprod."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/S0021-9258(19)75945-6","article-title":"Androgen repression of the production of a 29-kilodalton protein and its mRNA in the rat ventral prostate","volume":"262","author":"Saltzman","year":"1987","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1002\/pros.20748","article-title":"Chronic azacitidine treatment results in differentiating effects, sensitizes against bicalutamide in androgen-independent prostate cancer cells","volume":"68","author":"Gravina","year":"2008","journal-title":"Prostate"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1093\/toxsci\/60.1.132","article-title":"Maternal exposure to a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppressed the development of reproductive organs of male rats: Dose-dependent increase of mRNA levels of 5\u03b1-reductase type 2 in contrast to decrease of androgen receptor in the pubertal ventral prostate","volume":"60","author":"Ohsako","year":"2001","journal-title":"Toxicol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1477-7827-8-37","article-title":"Genome-wide profiling of gene expression in the epididymis of \u03b1-chlorohydrin-induced infertile rats using an oligonucleotide microarray","volume":"8","author":"Xie","year":"2010","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nmeth.1322","article-title":"Universal sample preparation method for proteome analysis","volume":"6","author":"Zougman","year":"2009","journal-title":"Nat. Methods"},{"key":"ref_32","unstructured":"BioBam company Functional Annotation and Genomics. Available online: http:\/\/www.blast2go.org."},{"key":"ref_33","unstructured":"National Institute of Allergy and Infectious Diseases (NIAID), NIH DAVID Bioinformatics Resources 6.7, Available online: http:\/\/david.abcc.ncifcrf.gov."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/21\/5\/602\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:23:42Z","timestamp":1760210622000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/21\/5\/602"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,11]]},"references-count":33,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2016,5]]}},"alternative-id":["molecules21050602"],"URL":"https:\/\/doi.org\/10.3390\/molecules21050602","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,11]]}}}