{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T14:05:17Z","timestamp":1740146717418,"version":"3.37.3"},"reference-count":99,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:00:00Z","timestamp":1619654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005961","name":"Universidad Nacional de Cuyo","doi-asserted-by":"publisher","award":["M066"],"award-info":[{"award-number":["M066"]}],"id":[{"id":"10.13039\/501100005961","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002790","name":"Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["1153952"],"award-info":[{"award-number":["1153952"]}],"id":[{"id":"10.13039\/501100002790","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>In the epididymis, lysosomal proteins of the epithelial cells are normally targeted from the Golgi apparatus to lysosomes for degradation, although their secretion into the epididymal lumen has been documented and associated with sperm maturation. In this study, cathepsin D (CatD) and prosaposin (PSAP) were examined in adult epididymis of control, and 2-day castrated rats without (Ct) and with testosterone replacement (Ct+T) to evaluate their expression and regulation within epididymal epithelial cells. By light microscope-immunocytochemistry, a quantitative increase in size of lysosomes in principal cells of Ct animals was noted from the distal initial segment to the proximal cauda. Androgen replacement did not restore the size of lysosomes to control levels. Western blot analysis revealed a significant increase in CatD expression in the epididymis of Ct animals, which suggested an upregulation of its expression in principal cells; androgens restored levels of CatD to that of controls. In contrast, PSAP expression in Ct animals was not altered from controls. Additionally, an increase in procathepsin D levels was noted from samples of the epididymal fluid of Ct compared to control animals, accompanied by an increased complex formation with PSAP. Moreover, an increased oligomerization of prosaposin was observed in the epididymal lumen of Ct rats, with changes reverted to controls in Ct+T animals. Taken together these data suggest castration causes an increased uptake of substrates that are acted upon by CatD in lysosomes of principal cells and in the lumen by procathepsin D. These substrates may be derived from apoptotic cells noted in the lumen of proximal regions and possibly by degenerating sperm in distal regions of the epididymis of Ct animals. Exploring the mechanisms by which lysosomal enzymes are synthesized and secreted by the epididymis may help resolve some of the issues originating from epididymal dysfunctions with relevance to sperm maturation.<\/jats:p>","DOI":"10.1371\/journal.pone.0250454","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T17:43:26Z","timestamp":1619718206000},"page":"e0250454","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Castration causes an increase in lysosomal size and upregulation of cathepsin D expression in principal cells along with increased secretion of procathepsin D and prosaposin oligomers in adult rat epididymis"],"prefix":"10.1371","volume":"16","author":[{"given":"Lorena","family":"Carvelli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea Carolina","family":"Aguilera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leila","family":"Zyla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura Luc\u00eda","family":"Pereyra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos R.","family":"Morales","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louis","family":"Hermo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5579-5494","authenticated-orcid":true,"given":"Miguel A.","family":"Sosa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,4,29]]},"reference":[{"key":"pone.0250454.ref001","first-page":"999","volume-title":"The Physiology of Reproduction","author":"B Robaire","year":"1988"},{"key":"pone.0250454.ref002","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/978-1-4939-0817-2_8","article-title":"Role of posttranslational protein modifications in epididymal sperm maturation and extracellular quality control","volume":"759","author":"GA Cornwall","year":"2014","journal-title":"Adv Exp Med Biol"},{"key":"pone.0250454.ref003","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1111\/andr.12632","article-title":"Epithelial dynamics in the epididymis: role in the maturation, protection, and storage of spermatozoa","volume":"7","author":"S Breton","year":"2019","journal-title":"Andrology"},{"key":"pone.0250454.ref004","first-page":"259","volume-title":"Handbook of Physiology","author":"DW Hamilton","year":"1975"},{"key":"pone.0250454.ref005","doi-asserted-by":"crossref","first-page":"208","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":"HI Adamali","year":"1996","journal-title":"J Androl"},{"key":"pone.0250454.ref006","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/B978-0-12-397175-3.00017-X","volume-title":"The Epididymis. Knobil and Neill\u2019s Physiology of Reproduction: Two-Volume Set","author":"B Robaire","year":"2015"},{"key":"pone.0250454.ref007","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4103\/1008-682X.165946","article-title":"Regulation of epithelial function, differentiation, and remodeling in the epididymis","author":"S Breton","year":"2016","journal-title":"Asian Journal of Andrology"},{"key":"pone.0250454.ref008","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/ar.1091930209","article-title":"Short\u2010term effects of androgen withdrawal on the structure of different epithelial cells in the rat epididymis","volume":"193","author":"HDM Moore","year":"1979","journal-title":"Anat Rec"},{"key":"pone.0250454.ref009","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1002\/aja.1001710106","article-title":"Endocytosis in nonciliated epithelial cells of the ductuli efferentes in the rat","volume":"171","author":"L Hermo","year":"1984","journal-title":"Am J Anat"},{"key":"pone.0250454.ref010","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1002\/mrd.1007","article-title":"Biogenesis of lysosomes in Marshall cells and in cells of the male reproductive system","volume":"59","author":"C Morales","year":"2001","journal-title":"Mol Reprod Dev"},{"key":"pone.0250454.ref011","first-page":"81","volume-title":"The epididymis: from molecules to clinical practice: a comprehensive survey of the efferent ducts, the epidiymus, and the vas deferens","author":"L Hermo","year":"2002"},{"key":"pone.0250454.ref012","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/0092-8674(84)90223-X","article-title":"The mannose-6-phosphate receptor for lysosomal enzymes is concentrated in cis Golgi cisternae","volume":"36","author":"WJ Brown","year":"1984","journal-title":"Cell"},{"key":"pone.0250454.ref013","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1002\/j.1939-4640.1999.tb02536.x","article-title":"Cell- and region-specific localization of lysosomal and secretory proteins and endocytic receptors in epithelial cells of the cauda epididymidis and vas deferens of the adult rat","volume":"20","author":"S Andonian","year":"1999","journal-title":"J Androl"},{"key":"pone.0250454.ref014","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1002\/j.1939-4640.2003.tb02690.x","article-title":"Regulation of sulfated glycoprotein-1 and cathepsin D expression in adult rat epididymis","volume":"24","author":"L Hermo","year":"2003","journal-title":"J Androl"},{"key":"pone.0250454.ref015","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1002\/jcb.22622","article-title":"Castration induces changes in the cation-dependent mannose-6-phosphate receptor in rat epididymis: possible implications in secretion of lysosomal enzymes","volume":"110","author":"LF Carvelli","year":"2010","journal-title":"J Cell Biochem"},{"key":"pone.0250454.ref016","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.critrevonc.2008.02.008","article-title":"Cathepsin D-Many functions of one aspartic protease","author":"P Benes","year":"2008","journal-title":"Critical Reviews in Oncology\/Hematology"},{"volume-title":"European Journal of Physical and Health Education","year":"2014","author":"Z Khalkhali-Ellis","key":"pone.0250454.ref017"},{"key":"pone.0250454.ref018","doi-asserted-by":"crossref","first-page":"3430","DOI":"10.1002\/j.1460-2075.1994.tb06648.x","article-title":"Differential sorting of lysosomal enzymes in mannose 6-phosphate receptor-deficient fibroblasts","volume":"13","author":"T Ludwig","year":"1994","journal-title":"EMBO J"},{"key":"pone.0250454.ref019","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1111\/and.12065","article-title":"Testosterone influences the expression and distribution of the cation-dependent mannose-6-phosphate receptor in rat epididymis. Implications in the distribution of enzymes","volume":"46","author":"L Carvelli","year":"2014","journal-title":"Andrologia"},{"key":"pone.0250454.ref020","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.bbrc.2008.08.099","article-title":"Cathepsin D: A cellular roadmap","author":"N Zaidi","year":"2008","journal-title":"Biochem Biophys Res Commun"},{"key":"pone.0250454.ref021","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2152\/jmi.52.1","article-title":"Involvement of cathepsins in the invasion, metastasis and proliferation of cancer cells","author":"T Nomura","year":"2005","journal-title":"Journal of Medical Investigation"},{"key":"pone.0250454.ref022","doi-asserted-by":"crossref","first-page":"385","DOI":"10.2174\/187153009789839174","article-title":"Pleiotropic Effects of Cathepsin D","volume":"9","author":"A Vashishta","year":"2009","journal-title":"Endocrine, Metab Immune Disord\u2014Drug Targets"},{"key":"pone.0250454.ref023","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1095\/biolreprod62.6.1790","article-title":"Stallion epididymal fluid proteome: Qualitative and quantitative characterization; secretion and dynamic changes of major proteins","volume":"62","author":"S Fouchecourt","year":"2000","journal-title":"Biol Reprod"},{"key":"pone.0250454.ref024","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1095\/biolreprod41.5.941","article-title":"Sulfated glycoprotein-1 (saposin precursor) in the reproductive tract of the male rat","volume":"41","author":"SR Sylvester","year":"1989","journal-title":"Biol Reprod"},{"key":"pone.0250454.ref025","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1002\/ar.1092320310","article-title":"Immunocytochemical localization of sulfated glycoprotein\u20101 (SGP\u20101) and identification of its transcripts in epithelial cells of the extratesticular duct system of the rat","volume":"232","author":"L Hermo","year":"1992","journal-title":"Anat Rec"},{"key":"pone.0250454.ref026","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/S0022-2275(20)40540-1","article-title":"Saposins: Structure, function, distribution, and molecular genetics","author":"Y Kishimoto","year":"1992","journal-title":"Journal of Lipid Research"},{"key":"pone.0250454.ref027","doi-asserted-by":"crossref","first-page":"6430","DOI":"10.1093\/emboj\/cdg629","article-title":"The lysosomal trafficking of sphingolipid activator proteins (SAPs) is mediated by sortilin","volume":"22","author":"S Lefrancois","year":"2003","journal-title":"EMBO J"},{"key":"pone.0250454.ref028","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/S0006-291X(05)80236-0","article-title":"Secretion of sphingolipid hydrolase activator precursor, prosaposin","volume":"176","author":"T Hineno","year":"1991","journal-title":"Biochem Biophys Res Commun"},{"key":"pone.0250454.ref029","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1016\/j.yexcr.2011.07.017","article-title":"Prosaposin sorting is mediated by oligomerization","volume":"317","author":"L Yuan","year":"2011","journal-title":"Exp Cell Res"},{"key":"pone.0250454.ref030","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1194\/jlr.R032326","article-title":"Sterols in spermatogenesis and sperm maturation","volume":"54","author":"R Keber","year":"2013","journal-title":"J Lipid Res"},{"key":"pone.0250454.ref031","first-page":"742","article-title":"Posttesticular sperm maturation, infertility, and hypercholesterolemia","author":"M Whitfield","year":"2015","journal-title":"Asian Journal of Andrology"},{"key":"pone.0250454.ref032","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/aja.1001740305","article-title":"Immunodissection of sperm surface modifications during epididymal maturation","volume":"174","author":"EM Eddy","year":"1985","journal-title":"Am J Anat"},{"key":"pone.0250454.ref033","first-page":"85","article-title":"Role of luminal fluid glycosyltransferases and glycosidases in the modification of rat sperm plasma membrane glycoproteins during epididymal maturation","volume":"53","author":"DR Tulsiani","year":"1998","journal-title":"J Reprod Fertil Suppl"},{"key":"pone.0250454.ref034","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1002\/j.1939-4640.1985.tb00840.x","article-title":"The origin of some acid hydrolases of the fluid of the rat cauda epididymidis","volume":"6","author":"LS Mayorga","year":"1985","journal-title":"J Androl"},{"key":"pone.0250454.ref035","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1080\/01485010252869289","article-title":"Compartmentalization of lysosomal enzymes in cauda epididymis of normal and castrated rats","volume":"48","author":"SA Belmonte","year":"2002","journal-title":"Arch Androl"},{"key":"pone.0250454.ref036","first-page":"103","article-title":"Molecular events that regulate mammalian fertilization","volume":"63","author":"DR Tulsiani","year":"2011","journal-title":"Minerva Ginecol"},{"key":"pone.0250454.ref037","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1439-0272.1975.tb01233.x","article-title":"The Effect of Epididymal and Testicular Fluids on the Fertilising Capacity of Testicular and Epididymal Spermatozoa","volume":"7","author":"TG Cooper","year":"1975","journal-title":"Andrologia"},{"key":"pone.0250454.ref038","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1093\/humupd\/dmn055","article-title":"New insights into epididymal biology and function","volume":"15","author":"GA Cornwall","year":"2009","journal-title":"Hum Reprod Update"},{"key":"pone.0250454.ref039","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1679\/aohc.52.299","article-title":"Early Degeneration of the Epithelial Cells in the Initial Segment of the Epididymal Duct in Mice after Efferent Duct Cutting","volume":"52","author":"K Abe","year":"1989","journal-title":"Arch Histol Cytol"},{"key":"pone.0250454.ref040","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1210\/endo.139.4.5888","article-title":"Orchidectomy induces a wave of apoptotic cell death in the epididymis","volume":"139","author":"X Fan","year":"1998","journal-title":"Endocrinology"},{"key":"pone.0250454.ref041","first-page":"211","article-title":"Regulation of apoptotic cell death in the rat epididymis","volume":"53","author":"B Robaire","year":"1998","journal-title":"J Reprod Fertil Suppl"},{"key":"pone.0250454.ref042","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1002\/j.1939-4640.2004.tb02760.x","article-title":"Postnatal development and regulation of beta-hexosaminidase in epithelial cells of the rat epididymis","volume":"25","author":"L Hermo","year":"2004","journal-title":"J Androl"},{"key":"pone.0250454.ref043","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1095\/biolreprod20.2.162","article-title":"Failure of exogenous androgen to prevent regression of the initial segments of the rat epididymis after efferent duct ligation or orchidectomy","volume":"20","author":"DW Fawcett","year":"1979","journal-title":"Biol Reprod"},{"key":"pone.0250454.ref044","first-page":"47","article-title":"Testicular regulation of epididymal gene expression","volume":"53","author":"BT Hinton","year":"1998","journal-title":"J Reprod Fertil Suppl"},{"key":"pone.0250454.ref045","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/978-1-4612-2106-7_15","volume-title":"The Testis","author":"BT Hinton","year":"2000"},{"key":"pone.0250454.ref046","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1210\/en.2002-220705","article-title":"Gene expression is differentially regulated in the epididymis after orchidectomy","volume":"144","author":"N Ezer","year":"2003","journal-title":"Endocrinology"},{"key":"pone.0250454.ref047","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1095\/biolreprod52.2.226","article-title":"Regulation of epididymal epithelial cell functions","volume":"52","author":"B Robaire","year":"1995","journal-title":"Biol Reprod"},{"key":"pone.0250454.ref048","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1111\/j.1745-7262.2007.00316.x","article-title":"Androgenic regulation of novel genes in the epididymis","volume":"9","author":"B Robaire","year":"2007","journal-title":"Asian J Androl"},{"key":"pone.0250454.ref049","doi-asserted-by":"crossref","first-page":"592","DOI":"10.2164\/jandrol.111.014266","article-title":"Androgen action in the epididymis","volume":"32","author":"B Robaire","year":"2011","journal-title":"J Androl"},{"key":"pone.0250454.ref050","doi-asserted-by":"crossref","first-page":"17188","DOI":"10.1074\/jbc.M200343200","article-title":"The lysosomal transport of prosaposin requires the conditional interaction of its highly conserved d domain with sphingomyelin","volume":"277","author":"S Lefrancois","year":"2002","journal-title":"J Biol Chem"},{"key":"pone.0250454.ref051","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of structural proteins during the assembly of the head of bacteriophage T4","volume":"227","author":"UK Laemmli","year":"1970","journal-title":"Nature"},{"key":"pone.0250454.ref052","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0003-2697(81)90281-5","article-title":"\u201cWestern blotting\u201d: electrophoretic transfer of proteins from sodium dodecyl sulfate\u2014polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A","volume":"112","author":"WN Burnette","year":"1981","journal-title":"Anal Biochem"},{"key":"pone.0250454.ref053","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.bbrc.2005.03.038","article-title":"Binding of AP-2 adaptor complex to brain membrane is regulated by phosphorylation of proteins","volume":"330","author":"A Alberdi","year":"2005","journal-title":"Biochem Biophys Res Commun"},{"key":"pone.0250454.ref054","doi-asserted-by":"crossref","first-page":"784","DOI":"10.2164\/jandrol.107.002980","article-title":"Structural alterations of epididymal epithelial cells in cathepsin A-deficient mice affect the blood-epididymal barrier and lead to altered sperm motility","volume":"28","author":"L Hermo","year":"2007","journal-title":"J Androl"},{"key":"pone.0250454.ref055","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1002\/ar.1092320206","article-title":"Epithelial cells of the epididymis show regional variations with respect to the secretion or endocytosis of immobilin as revealed by light and electron microscope immunocytochemistry","volume":"232","author":"L Hermo","year":"1992","journal-title":"Anat Rec"},{"key":"pone.0250454.ref056","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1006\/abbi.1997.9958","article-title":"Lysosomal proteolysis of prosaposin, the precursor of saposins (sphingolipid activator proteins): its mechanism and inhibition by ganglioside","volume":"341","author":"M Hiraiwa","year":"1997","journal-title":"Arch Biochem Biophys"},{"key":"pone.0250454.ref057","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1042\/BJ20040175","article-title":"Purified recombinant human prosaposin forms oligomers that bind procathepsin D and affect its autoactivation","volume":"383","author":"MM Gopalakrishnan","year":"2004","journal-title":"Biochem J"},{"key":"pone.0250454.ref058","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.semcdb.2014.03.034","article-title":"Endosome maturation, transport and functions","author":"CC Scott","year":"2014","journal-title":"Seminars in Cell and Developmental Biology"},{"key":"pone.0250454.ref059","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1002\/j.1939-4640.1999.tb03385.x","article-title":"I. Abnormalities in cells of the testis, efferent ducts, and epididymis in juvenile and adult mice with \u03b2-hexosaminidase A and B deficiency","volume":"20","author":"HI Adamali","year":"1999","journal-title":"J Androl"},{"key":"pone.0250454.ref060","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1002\/j.1939-4640.1999.tb03386.x","article-title":"II. Characterization and development of the regional- and cellular- specific abnormalities in the epididymis of mice with \u03b2-hexosaminidase A deficiency","volume":"20","author":"HI Adamali","year":"1999","journal-title":"J Androl"},{"key":"pone.0250454.ref061","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/mrd.10359","article-title":"Characterization of Cell- and Region-Specific Abnormalities in the Epididymis of Cathepsin A Deficient Mice","volume":"66","author":"N Korah","year":"2003","journal-title":"Mol Reprod Dev"},{"key":"pone.0250454.ref062","first-page":"297","volume-title":"The epididymis: from molecules to clinical practice: a comprehensive survey of the efferent ducts, the epidiymus, and the vas deferens","author":"N Ezer","year":"2002"},{"key":"pone.0250454.ref063","article-title":"Androgenic regulation of beta-defensins in the mouse epididymis","volume":"12","author":"SG Hu","year":"2014","journal-title":"Reprod Biol Endocrinol"},{"key":"pone.0250454.ref064","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1071\/RD13323","article-title":"New insight into the castrated mouse epididymis based on comparative proteomics","volume":"27","author":"X Liu","year":"2015","journal-title":"Reprod Fertil Dev"},{"key":"pone.0250454.ref065","doi-asserted-by":"crossref","first-page":"200","DOI":"10.2164\/jandrol.108.006171","article-title":"Effect of testosterone on epithelial cell proliferation in the regressed rat epididymis","volume":"30","author":"M Hamzeh","year":"2009","journal-title":"J Androl"},{"key":"pone.0250454.ref066","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/S0022-5347(17)54059-8","article-title":"Activities of cathepsin D in rat prostate during castration induced involution","volume":"127","author":"ET Tanabe","year":"1982","journal-title":"J Urol"},{"key":"pone.0250454.ref067","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1530\/rep.0.1250871","article-title":"Association of segmentation of the epididymal interstitium with segmented tubule function in rats and mice","volume":"125","author":"TT Turner","year":"2003","journal-title":"Reproduction"},{"key":"pone.0250454.ref068","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1095\/biolreprod.106.057323","article-title":"The rat epididymal transcriptome: Comparison of segmental gene expression in the rat and mouse epididymides","volume":"76","author":"SA Jelinsky","year":"2007","journal-title":"Biol Reprod"},{"key":"pone.0250454.ref069","article-title":"Is the epididymis a series of organs placed side by side?","author":"RF Domeniconi","year":"2016","journal-title":"Biology of Reproduction"},{"key":"pone.0250454.ref070","doi-asserted-by":"crossref","first-page":"R91","DOI":"10.1530\/REP-15-0533","article-title":"Segment-specific regulation of epididymal gene expression","author":"P Sipil\u00e4","year":"2016","journal-title":"Reproduction"},{"key":"pone.0250454.ref071","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1093\/abbs\/gmp116","article-title":"Comparative profiling of genes and miRNAs expressed in the newborn, young adult, and aged human epididymides","volume":"42","author":"J Zhang","year":"2010","journal-title":"Acta Biochim Biophys Sin (Shanghai)"},{"key":"pone.0250454.ref072","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0034996","article-title":"Role of microRNAs in controlling gene expression in different segments of the human epididymis","volume":"7","author":"C Belleann\u00e9e","year":"2012","journal-title":"PLoS One"},{"key":"pone.0250454.ref073","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1111\/andr.12640","article-title":"Profiling of epididymal small non-protein-coding RNAs","author":"B Nixon","year":"2019","journal-title":"Andrology"},{"key":"pone.0250454.ref074","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1002\/(SICI)1098-2795(199906)53:2<188::AID-MRD8>3.0.CO;2-O","article-title":"p53 Independent, region-specific epithelial apoptosis is induced in the rat epididymis by deprivation of luminal factors","author":"TT Turner","year":"1999","journal-title":"Molecular Reproduction and Development"},{"key":"pone.0250454.ref075","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1507\/endocrj.49.75","article-title":"Castration induces apoptosis in the mouse epididymis during postnatal development","volume":"49","author":"Y Takagi-Morishita","year":"2002","journal-title":"Endocr J"},{"key":"pone.0250454.ref076","article-title":"Role of testicular luminal factors on basal cell elongation and proliferation in the mouse epididymis","volume":"92","author":"B Kim","year":"2015","journal-title":"Biol Reprod"},{"key":"pone.0250454.ref077","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1093\/biolre\/ioz152","article-title":"Androgens are essential for epithelial cell recovery after efferent duct ligation in the initial segment of the mouse epididymis","volume":"102","author":"B Kim","year":"2020","journal-title":"Biol Reprod"},{"key":"pone.0250454.ref078","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1210\/endo-93-2-391","article-title":"Effect of hypophysectomy, castration and androgen replacement upon the fertilizing ability of rat epididymal spermatozoa","volume":"93","author":"ALMB Dyson","year":"1973","journal-title":"Endocrinology"},{"key":"pone.0250454.ref079","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/j.1939-4640.1993.tb00366.x","article-title":"Immunocytochemical Localization of the Yf Subunit of Glutathione S\u2010Transferase P Shows Regional Variation in the Staining of Epithelial Cells of the Testis, Efferent Ducts, and Epididymis of the Male Rat","volume":"14","author":"JP Veri","year":"1993","journal-title":"J Androl"},{"key":"pone.0250454.ref080","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1016\/j.cell.2008.10.020","article-title":"Transepithelial Projections from Basal Cells Are Luminal Sensors in Pseudostratified Epithelia","volume":"135","author":"WWC Shum","year":"2008","journal-title":"Cell"},{"key":"pone.0250454.ref081","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1530\/REP-10-0493","article-title":"A dense network of dendritic cells populates the murine epididymis","volume":"141","author":"N Da Silva","year":"2011","journal-title":"Reproduction"},{"key":"pone.0250454.ref082","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1530\/REP-12-0510","article-title":"Plasticity of basal cells during postnatal development in the rat epididymis","volume":"146","author":"WWC Shum","year":"2013","journal-title":"Reproduction"},{"key":"pone.0250454.ref083","article-title":"Epithelial basal cells are distinct from dendritic cells and macrophages in the mouse epididymis","volume":"90","author":"WW Shum","year":"2014","journal-title":"Biol Reprod"},{"key":"pone.0250454.ref084","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":"TB Smith","year":"2014","journal-title":"Andrology"},{"key":"pone.0250454.ref085","doi-asserted-by":"crossref","DOI":"10.1095\/biolreprod.115.133967","article-title":"Isolated rat epididymal basal cells share common properties with adult stem cells","volume":"93","author":"M Mandon","year":"2015","journal-title":"Biol Reprod"},{"key":"pone.0250454.ref086","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1002\/ar.1092290306","article-title":"Immunocytochemical localization of cathepsin D in rat ventral prostate: Evidence for castration\u2010induced expression of cathepsin D in basal cells","volume":"229","author":"MJ Wilson","year":"1991","journal-title":"Anat Rec"},{"key":"pone.0250454.ref087","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.mce.2005.12.022","article-title":"Human epididymal secretome and proteome","volume":"250","author":"JL Dacheux","year":"2006","journal-title":"Mol Cell Endocrinol"},{"key":"pone.0250454.ref088","article-title":"The immunoexpression of FSH-R in the ductuli efferentes and the epididymis of men and Rat: effect of FSH on the morphology and steroidogenic activity of rat epididymal epithelial cells in vitro","volume":"2010","author":"M \u015awider-Al-Amawi","year":"2010","journal-title":"J Biomed Biotechnol"},{"key":"pone.0250454.ref089","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1530\/acta.0.1140084","article-title":"Tamoxifen does not block the inhibitory effect of testosterone on FSH release in rats","volume":"114","author":"P Negri-Cesi","year":"1987","journal-title":"Acta Endocrinol (Copenh)"},{"key":"pone.0250454.ref090","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1242\/jcs.111.17.2539","article-title":"Endocytosis of pro-cathepsin D into breast cancer cells is mostly independent of mannose-6-phosphate receptors","volume":"111","author":"V Laurent-Matha","year":"1998","journal-title":"J Cell Sci"},{"key":"pone.0250454.ref091","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1242\/jcs.112.10.1591","article-title":"Alternative mechanisms for trafficking of lysosomal enzymes in mannose 6- phosphate receptor-deficient mice are cell type-specific","volume":"112","author":"F Dittmer","year":"1999","journal-title":"J Cell Sci"},{"key":"pone.0250454.ref092","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1002\/jcb.21207","article-title":"Prosaposin is a novel androgen-regulated gene in prostate cancer cell line LNCaP","volume":"101","author":"S Koochekpour","year":"2007","journal-title":"J Cell Biochem"},{"key":"pone.0250454.ref093","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1097\/00029330-200802020-00016","article-title":"Metabolism of adrenal androgen and its impacts on prostate cancer after castration","volume":"121","author":"M Hu","year":"2008","journal-title":"Chin Med J (Engl)"},{"key":"pone.0250454.ref094","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1002\/j.1939-4640.1992.tb00314.x","article-title":"Testicular Regulation of Epididymal Protein Secretion","volume":"13","author":"MK Holland","year":"1992","journal-title":"J Androl"},{"key":"pone.0250454.ref095","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/nrm732","article-title":"Secretory lysosomes","author":"EJ Blott","year":"2002","journal-title":"Nature Reviews Molecular Cell Biology"},{"key":"pone.0250454.ref096","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1139\/o90-075","article-title":"Levels of sulfogalactosylglycerolipid in capacitated motile and immotile mouse spermatozoa","volume":"68","author":"N Tanphaichitr","year":"1990","journal-title":"Biochem Cell Biol"},{"key":"pone.0250454.ref097","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1095\/biolreprod66.6.1820","article-title":"Binding of arylsulfatase A to mouse sperm inhibits gamete interaction and induces the acrosome reaction","volume":"66","author":"E Carmona","year":"2002","journal-title":"Biol Reprod"},{"key":"pone.0250454.ref098","doi-asserted-by":"crossref","first-page":"9372","DOI":"10.1074\/jbc.M809457200","article-title":"Saposin B-dependent reconstitution of arylsulfatase A activity in vitro and in cell culture models of metachromatic leukodystrophy","volume":"284","author":"U Matzner","year":"2009","journal-title":"J Biol Chem"},{"key":"pone.0250454.ref099","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1095\/biolreprod.102.010231","article-title":"Acquisition of arylsulfatase A onto the mouse sperm surface during epididymal transit","volume":"69","author":"W Weerachatyanukul","year":"2003","journal-title":"Biol Reprod"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0250454","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T00:29:53Z","timestamp":1698971393000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0250454"}},"subtitle":[],"editor":[{"given":"Suresh","family":"Yenugu","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,4,29]]},"references-count":99,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0250454","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2021,4,29]]}}}