{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T09:13:26Z","timestamp":1788599606631,"version":"build-2803163510"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:p>Non-obstructive azoospermia (NOA) and obstructive azoospermia (OA) are the main classifications of severe male infertility, but the molecular mechanism of NOA remains poorly understood. This study aimed to identify potential biomarkers and pathological mechanisms by comparing the proteomic differences in testicular tissues of NOA and OA patients. Through proteomic analysis based on liquid chromatography-tandem mass spectrometry (LC-MS\/MS) of testicular samples from 5 NOA patients and 5 OA patients, we identified 5264 proteins, among which 717 differentially expressed proteins (DEPs) were found between the two groups (242 upregulated and 475 downregulated in NOA). Bioinformatics analysis indicated that these DEPs were significantly associated with reproductive development, gametogenesis, and cell structural stability. On the basis of this, six candidate proteins, including dysferlin (DYSF), myoferlin (MYOF), mitsugumin 53 (MG53), cluster of differentiation 63 (CD63), caveolin-3 (CAV3), and calpain-3 (CAPN3), were selected from the DEPs and verified in an expanded sample set (37 NOA cases and 28 OA cases) through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, confirming their dysregulation in NOA. These findings provide new proteomic insights into NOA, highlighting the disruption of membrane repair and structural pathways, and offer potential biomarkers for understanding its pathogenesis.<\/jats:p>","DOI":"10.4103\/aja2025114","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T07:00:17Z","timestamp":1780038017000},"page":"603-612","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Proteomic insights into azoospermia: protein differences in testicular tissue between non-obstructive and obstructive azoospermia patients"],"prefix":"10.4103","volume":"28","author":[{"given":"Zhi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital, Xinjiang Medical University, Urumqi 830011, China"},{"name":"Xinjiang Key Laboratory of Clinical Drug Research, Urumqi 830011, China"},{"name":"Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Dong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, 830011, China"},{"name":"Xinjiang Clinical Research Center of Urogenital Diseases, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Min","family":"Shao","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Xuan","family":"Zheng","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Xinjiang Medical University, Urumqi 830054, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Qiang","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng-Qing","family":"An","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, 830011, China"},{"name":"Xinjiang Clinical Research Center of Urogenital Diseases, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Hua","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital, Xinjiang Medical University, Urumqi 830011, China"},{"name":"Xinjiang Key Laboratory of Clinical Drug Research, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"R1-20260905","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.eururo.2025.02.026","article-title":"European Association of Urology guidelines on male sexual and reproductive health: 2025 update on male infertility","volume":"87","author":"Minhas","year":"2025","journal-title":"Eur Urol"},{"key":"R2-20260905","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1097\/JU.0000000000004180","article-title":"Updates to male infertility: AUA\/ASRM guideline (2024)","volume":"212","author":"Brannigan","year":"2024","journal-title":"J Urol"},{"key":"R3-20260905","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41585-023-00837-9","article-title":"Molecular mechanisms of cellular dysfunction in testes from men with non-obstructive azoospermia","volume":"21","author":"Piechka","year":"2024","journal-title":"Nat Rev Urol"},{"key":"R4-20260905","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1097\/MOU.0000000000001055","article-title":"Modern surgical treatment of azoospermia","volume":"33","author":"Brant","year":"2023","journal-title":"Curr Opin Urol"},{"key":"R5-20260905","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1007\/s43032-022-01115-6","article-title":"Cell-based therapy approaches in treatment of non-obstructive azoospermia","volume":"30","author":"Roshandel","year":"2023","journal-title":"Reprod Sci"},{"key":"R6-20260905","doi-asserted-by":"crossref","first-page":"370","DOI":"10.4103\/aja202454","article-title":"A review of testicular histopathology in nonobstructive azoospermia","volume":"27","author":"Mostafa","year":"2025","journal-title":"Asian J Androl"},{"key":"R7-20260905","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1080\/14789450.2024.2327553","article-title":"Bringing proteomics to bear on male fertility: key lessons","volume":"21","author":"Parkes","year":"2024","journal-title":"Expert Rev Proteomics"},{"key":"R8-20260905","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1093\/humrep\/dead170","article-title":"Proteomics of human spermatozoa","volume":"38","author":"Castillo","year":"2023","journal-title":"Hum Reprod"},{"key":"R9-20260905","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1080\/14789450.2021.2010548","article-title":"Protein markers of spermatogenesis and their potential use in the management of azoospermia","volume":"18","author":"Araujo","year":"2021","journal-title":"Expert Rev Proteomics"},{"key":"R12-20260905","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1002\/prot.21018","article-title":"Prediction of protein subcellular localization","volume":"64","author":"Yu","year":"2006","journal-title":"Proteins"},{"key":"R13-20260905","doi-asserted-by":"crossref","first-page":"5683","DOI":"10.1038\/s41467-020-19414-4","article-title":"Single-cell analysis of developing and azoospermia human testicles reveals central role of sertoli cells","volume":"11","author":"Zhao","year":"2020","journal-title":"Nat Commun"},{"key":"R14-20260905","doi-asserted-by":"crossref","first-page":"225","DOI":"10.4274\/BMJ.galenos.2024.2024.1-2","article-title":"Use of volumetric apparent diffusion coefficient to distinguish between obstructive and non-obstructive azoospermia: a case-control study","volume":"20","author":"Ghafoori","year":"2024","journal-title":"Med J Bakirkoy"},{"key":"R15-20260905","doi-asserted-by":"crossref","first-page":"298","DOI":"10.4103\/aja202475","article-title":"Differentiation between nonobstructive azoospermia and obstructive azoospermia: then and now","volume":"27","author":"Hubbard","year":"2025","journal-title":"Asian J Androl"},{"key":"R16-20260905","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1007\/s10815-021-02313-y","article-title":"FSH levels and testicular volumes are associated with the severity of testicular histopathology in men with non-obstructive azoospermia","volume":"38","author":"Kavoussi","year":"2021","journal-title":"J Assist Reprod Genet"},{"key":"R17-20260905","doi-asserted-by":"crossref","first-page":"274","DOI":"10.4103\/aja202181","article-title":"Endocrine aberrations of human nonobstructive azoospermia","volume":"24","author":"Tao","year":"2022","journal-title":"Asian J Androl"},{"key":"R18-20260905","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1093\/humrep\/det068","article-title":"Sertoli cells from non-obstructive azoospermia and obstructive azoospermia patients show distinct morphology, Raman spectrum and biochemical phenotype","volume":"28","author":"Ma","year":"2013","journal-title":"Hum Reprod"},{"key":"R19-20260905","doi-asserted-by":"crossref","first-page":"104686","DOI":"10.1016\/j.jprot.2022.104686","article-title":"Comparative proteomics analysis of human FFPE testicular tissues reveals new candidate biomarkers for distinction among azoospermia types and subtypes","volume":"267","author":"Davalieva","year":"2022","journal-title":"J Proteomics"},{"key":"R20-20260905","doi-asserted-by":"crossref","first-page":"12164","DOI":"10.1038\/s41598-023-38947-4","article-title":"Identification and verification of potential biomarkers in sertoli cell-only syndrome via bioinformatics analysis","volume":"13","author":"Jiang","year":"2023","journal-title":"Sci Rep"},{"key":"R21-20260905","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1007\/s00018-025-05678-w","article-title":"Micro-proteomics reveals distinct protein profiles and SPARC\/FGF2\/CDH1 regulation of human Sertoli cells between Sertoli cell-only syndrome and normal men","volume":"82","author":"Du","year":"2025","journal-title":"Cell Mol Life Sci"},{"key":"R22-20260905","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.gendis.2020.09.004","article-title":"Human obstructive (postvasectomy) and nonobstructive azoospermia \u2013 insights from scRNA-Seq and transcriptome analysis","volume":"9","author":"Chen","year":"2022","journal-title":"Genes Dis"},{"key":"R23-20260905","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1038\/s43587-025-00824-2","article-title":"Single-cell transcriptomic atlas of the human testis across the reproductive lifespan","volume":"5","author":"Cui","year":"2025","journal-title":"Nat Aging"},{"key":"R24-20260905","doi-asserted-by":"crossref","first-page":"1327800","DOI":"10.3389\/fendo.2024.1327800","article-title":"Proteomic biomarkers in seminal plasma as predictors of reproductive potential in azoospermic men","volume":"15","author":"Fietz","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"key":"R25-20260905","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.3390\/cells12222648","article-title":"Mechanisms of endothelial cell membrane repair: progress and perspectives","volume":"12","author":"Zha","year":"2023","journal-title":"Cells"},{"key":"R26-20260905","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1113\/JP282648","article-title":"The C2 domains of dysferlin: roles in membrane localization, Ca2+ signalling and sarcolemmal repair","volume":"600","author":"Muriel","year":"2022","journal-title":"J Physiol Lond"},{"key":"R27-20260905","doi-asserted-by":"crossref","first-page":"9650","DOI":"10.1038\/s41467-024-53773-6","article-title":"Cryo-EM structures of the membrane repair protein dysferlin","volume":"15","author":"Huang","year":"2024","journal-title":"Nat Commun"},{"key":"R28-20260905","doi-asserted-by":"crossref","first-page":"eade7607","DOI":"10.1126\/sciadv.ade7607","article-title":"Testis-enriched ferlin, FER1L5, is required for Ca2+-activated acrosome reaction and male fertility","volume":"9","author":"Morohoshi","year":"2023","journal-title":"Sci Adv"},{"key":"R29-20260905","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Tissue-based map of the human proteome","volume":"347","author":"Uhlen","year":"2015","journal-title":"Science"},{"key":"R30-20260905","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/j.ymthe.2020.02.006","article-title":"AMPK complex activation promotes sarcolemmal repair in dysferlinopathy","volume":"28","author":"Ono","year":"2020","journal-title":"Mol Ther"},{"key":"R31-20260905","first-page":"7365913","article-title":"Myoferlin, a membrane protein with emerging oncogenic roles","author":"Dong","year":"2019","journal-title":"Biomed Res Int 2019"},{"key":"R32-20260905","doi-asserted-by":"crossref","first-page":"3926","DOI":"10.1038\/s44318-025-00463-8","article-title":"Structural insights into lipid membrane binding by human ferlins","volume":"44","author":"Cretu","year":"2025","journal-title":"EMBO J"},{"key":"R33-20260905","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1124\/mol.117.108241","article-title":"MG53: biological function and potential as a therapeutic target","volume":"92","author":"Zhang","year":"2017","journal-title":"Mol Pharmacol"},{"key":"R34-20260905","doi-asserted-by":"crossref","first-page":"1377025","DOI":"10.3389\/fphys.2024.1377025","article-title":"MG53\/TRIM72: multi-organ repair protein and beyond","volume":"15","author":"Wang","year":"2024","journal-title":"Front Physiol"},{"key":"R35-20260905","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s12943-021-01418-3","article-title":"MG53 suppresses tumor progression and stress granule formation by modulating G3BP2 activity in non-small cell lung cancer","volume":"20","author":"Li","year":"2021","journal-title":"Mol Cancer"},{"key":"R36-20260905","doi-asserted-by":"crossref","first-page":"29449","DOI":"10.1038\/s41598-024-81021-w","article-title":"The extracellular vesicle tetraspanin CD63 journey from the testis through the epididymis to mature bull sperm","volume":"14","author":"Jankovicov\u00e1","year":"2024","journal-title":"Sci Rep"},{"key":"R37-20260905","doi-asserted-by":"crossref","first-page":"e70006","DOI":"10.1002\/jev2.70006","article-title":"Isolation of CD63-positive epididymosomes from human semen and its application in improving sperm function","volume":"13","author":"Luo","year":"2024","journal-title":"J Extracell Vesicles"},{"key":"R38-20260905","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1089\/scd.2019.0026","article-title":"Urine-derived stem cells facilitate endogenous spermatogenesis restoration of busulfan-induced nonobstructive azoospermic mice by paracrine exosomes","volume":"28","author":"Deng","year":"2019","journal-title":"Stem Cells Dev"},{"key":"R39-20260905","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/s41598-023-27898-5","article-title":"HA-tag CD63 is a novel conditional transgenic approach to track extracellular vesicle interactions with sperm and their transfer at conception","volume":"13","author":"Morgan","year":"2023","journal-title":"Sci Rep"},{"key":"R40-20260905","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1161\/CIRCULATIONAHA.122.063073","article-title":"Nitrative modification of caveolin-3: a novel mechanism of cardiac insulin resistance and a potential therapeutic target against ischemic heart failure in prediabetic animals","volume":"147","author":"Meng","year":"2023","journal-title":"Circulation"},{"key":"R41-20260905","doi-asserted-by":"crossref","first-page":"8736","DOI":"10.3390\/ijms21228736","article-title":"A role for caveolin-3 in the pathogenesis of muscular dystrophies","volume":"21","author":"Pradhan","year":"2020","journal-title":"Int J Mol Sci"},{"key":"R42-20260905","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1177\/22143602251345967","article-title":"Calpainopathy (limb-girdle muscular dystrophy type R1): clinical features, diagnostic approaches, and biotechnological treatment methods","volume":"12","author":"Bardakov","year":"2025","journal-title":"J Neuromuscular Dis"},{"key":"R43-20260905","first-page":"167918","article-title":"Deciphering the regulatory networks of human male germline development from embryo to adulthood","author":"Chen","year":"1871","journal-title":"Biochim Biophys Acta Mol Basis Dis 2025"},{"key":"R44-20260905","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/s41576-021-00370-8","article-title":"Integrating single-cell and spatial transcriptomics to elucidate intercellular tissue dynamics","volume":"22","author":"Longo","year":"2021","journal-title":"Nat Rev Genet"},{"key":"R45-20260905","doi-asserted-by":"crossref","first-page":"720","DOI":"10.3390\/antiox14060720","article-title":"Role of redox-induced protein modifications in spermatozoa in health and disease","volume":"14","author":"Onochie","year":"2025","journal-title":"Antioxidants (Basel)"}],"container-title":["Asian Journal of Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/aja2025114","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T09:00:42Z","timestamp":1788598842000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/aja2025114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":43,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.4103\/aja2025114","relation":{},"ISSN":["1008-682X","1745-7262"],"issn-type":[{"value":"1008-682X","type":"print"},{"value":"1745-7262","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]},"assertion":[{"value":"2025-04-29","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-05","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}