{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T13:33:56Z","timestamp":1794058436377,"version":"4.8.0"},"reference-count":47,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T00:00:00Z","timestamp":1713484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005363","name":"Universidad de Buenos Aires","doi-asserted-by":"publisher","award":["UBA 20020150100104BA"],"award-info":[{"award-number":["UBA 20020150100104BA"]}],"id":[{"id":"10.13039\/501100005363","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005363","name":"Universidad de Buenos Aires","doi-asserted-by":"publisher","award":["PICT 0497"],"award-info":[{"award-number":["PICT 0497"]}],"id":[{"id":"10.13039\/501100005363","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005363","name":"Universidad de Buenos Aires","doi-asserted-by":"publisher","award":["PICT 00671"],"award-info":[{"award-number":["PICT 00671"]}],"id":[{"id":"10.13039\/501100005363","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","award":["UBA 20020150100104BA"],"award-info":[{"award-number":["UBA 20020150100104BA"]}]},{"name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","award":["PICT 0497"],"award-info":[{"award-number":["PICT 0497"]}]},{"name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","award":["PICT 00671"],"award-info":[{"award-number":["PICT 00671"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Experimental autoimmune orchitis (EAO) is a well-established rodent model of organ-specific autoimmunity associated with infertility in which the testis immunohistopathology has been extensively studied. In contrast, analysis of testis biopsies from infertile patients associated with inflammation has been more limited. In this work, testicular biopsies from patients with idiopathic non-obstructive azoospermia diagnosed with hypospermatogenesis (HypoSp) [mild: n = 9, and severe: n = 11], with obstructive azoospermia and complete Sp (spermatogenesis) (control group, C, n = 9), and from Sertoli cell-only syndrome (SCOS, n = 9) were analyzed for the presence of immune cells, spermatogonia and Sertoli cell (SCs) alterations, and reproductive hormones levels. These parameters were compared with those obtained in rats with EAO. The presence of increased CD45+ cells in the seminiferous tubules (STs) wall and lumen in severe HypoSp is associated with increased numbers of apoptotic meiotic germ cells and decreased populations of undifferentiated and differentiated spermatogonia. The SCs showed an immature profile with the highest expression of AMH in patients with SCOS and severe HypoSp. In SCOS patients, the amount of SCs\/ST and Ki67+ SCs\/ST increased and correlated with high serum FSH levels and CD45+ cells. In the severe phase of EAO, immune cell infiltration and apoptosis of meiotic germ cells increased and the number of undifferentiated and differentiated spermatogonia was lowest, as previously reported. Here, we found that orchitis leads to reduced sperm number, viability, and motility. SCs were mature (AMH-) but increased in number, with Ki67+ observed in severely damaged STs and associated with the highest levels of FSH and inflammatory cells. Our findings demonstrate that in a scenario where a chronic inflammatory process is underway, FSH levels, immune cell infiltration, and immature phenotypes of SCs are associated with severe changes in spermatogenesis, leading to azoospermia. Furthermore, AMH and Ki67 expression in SCs is a distinctive marker of severe alterations of STs in human orchitis.<\/jats:p>","DOI":"10.3390\/biology13040278","type":"journal-article","created":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T06:28:09Z","timestamp":1713508089000},"page":"278","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Impaired Spermatogenesis in Infertile Patients with Orchitis and Experimental Autoimmune Orchitis in Rats"],"prefix":"10.3390","volume":"13","author":[{"given":"Mar\u00eda Sof\u00eda","family":"Amarilla","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas (INBIOMED), CONICET-Universidad de Buenos Aires, Paraguay 2155, Piso 10, Laboratorio 10, Ciudad Aut\u00f3noma de Buenos Aires C1421ABG, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leilane","family":"Glienke","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas (INBIOMED), CONICET-Universidad de Buenos Aires, Paraguay 2155, Piso 10, Laboratorio 10, Ciudad Aut\u00f3noma de Buenos Aires C1421ABG, Argentina"},{"name":"Departamento de Biolog\u00eda Celular, Facultad de Medicina, Universidad de Buenos Aires, C\u00e1tedra II de Histolog\u00eda, Paraguay 2155, Ciudad Aut\u00f3noma de Buenos Aires C1421ABG, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thaisy","family":"Munduruca Pires","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas (INBIOMED), CONICET-Universidad de Buenos Aires, Paraguay 2155, Piso 10, Laboratorio 10, Ciudad Aut\u00f3noma de Buenos Aires C1421ABG, Argentina"},{"name":"Departamento de Biolog\u00eda Celular, Facultad de Medicina, Universidad de Buenos Aires, C\u00e1tedra II de Histolog\u00eda, Paraguay 2155, Ciudad Aut\u00f3noma de Buenos Aires C1421ABG, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian Marcelo","family":"Sobarzo","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas (INBIOMED), CONICET-Universidad de Buenos Aires, Paraguay 2155, Piso 10, Laboratorio 10, Ciudad Aut\u00f3noma de Buenos Aires C1421ABG, Argentina"},{"name":"Departamento de Biolog\u00eda Celular, Facultad de Medicina, Universidad de Buenos Aires, C\u00e1tedra II de Histolog\u00eda, Paraguay 2155, Ciudad Aut\u00f3noma de Buenos Aires C1421ABG, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8992-7747","authenticated-orcid":false,"given":"Hern\u00e1n Gustavo","family":"Oxilia","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular, Facultad de Medicina, Universidad de Buenos Aires, C\u00e1tedra II de Histolog\u00eda, Paraguay 2155, Ciudad Aut\u00f3noma de Buenos Aires C1421ABG, Argentina"},{"name":"Anatom\u00eda Patol\u00f3gica, Hospital General de Agudos Parmenio Pi\u00f1ero, Varela 1301, Ciudad Aut\u00f3noma de Buenos Aires C1406ELA, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Florencia","family":"Fulco","sequence":"additional","affiliation":[{"name":"Hospital de Cl\u00ednicas General San Mart\u00edn, Av. C\u00f3rdoba 2351 (C1120AAR), Ciudad Aut\u00f3noma de Buenos Aires C1421ABG, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Rodr\u00edguez Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Hospital de Cl\u00ednicas General San Mart\u00edn, Av. C\u00f3rdoba 2351 (C1120AAR), Ciudad Aut\u00f3noma de Buenos Aires C1421ABG, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Bel\u00e9n","family":"Maio","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas (INBIOMED), CONICET-Universidad de Buenos Aires, Paraguay 2155, Piso 10, Laboratorio 10, Ciudad Aut\u00f3noma de Buenos Aires C1421ABG, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denisse","family":"Ferrer Vi\u00f1als","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas (INBIOMED), CONICET-Universidad de Buenos Aires, Paraguay 2155, Piso 10, Laboratorio 10, Ciudad Aut\u00f3noma de Buenos Aires C1421ABG, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Lustig","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas (INBIOMED), CONICET-Universidad de Buenos Aires, Paraguay 2155, Piso 10, Laboratorio 10, Ciudad Aut\u00f3noma de Buenos Aires C1421ABG, Argentina"},{"name":"Departamento de Biolog\u00eda Celular, Facultad de Medicina, Universidad de Buenos Aires, C\u00e1tedra II de Histolog\u00eda, Paraguay 2155, Ciudad Aut\u00f3noma de Buenos Aires C1421ABG, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia Ver\u00f3nica","family":"Jacobo","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas (INBIOMED), CONICET-Universidad de Buenos Aires, Paraguay 2155, Piso 10, Laboratorio 10, Ciudad Aut\u00f3noma de Buenos Aires C1421ABG, Argentina"},{"name":"Departamento de Biolog\u00eda Celular, Facultad de Medicina, Universidad de Buenos Aires, C\u00e1tedra II de Histolog\u00eda, Paraguay 2155, Ciudad Aut\u00f3noma de Buenos Aires C1421ABG, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8971-9833","authenticated-orcid":false,"given":"Mar\u00eda Susana","family":"Theas","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas (INBIOMED), CONICET-Universidad de Buenos Aires, Paraguay 2155, Piso 10, Laboratorio 10, Ciudad Aut\u00f3noma de Buenos Aires C1421ABG, Argentina"},{"name":"Departamento de Biolog\u00eda Celular, Facultad de Medicina, Universidad de Buenos Aires, C\u00e1tedra II de Histolog\u00eda, Paraguay 2155, Ciudad Aut\u00f3noma de Buenos Aires C1421ABG, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ijantimicag.2007.07.044","article-title":"Evaluation of Acute and Chronic Bacterial Prostatitis and Diagnostic Management of Chronic Prostatitis\/Chronic Pelvic Pain Syndrome with Special Reference to Infection\/Inflammation","volume":"31","author":"Weidner","year":"2008","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e13401","DOI":"10.1111\/and.13401","article-title":"High Prevalence of Urogenital Infection\/Inflammation in Patients with Azoospermia Does Not Impede Surgical Sperm Retrieval","volume":"51","author":"Pilatz","year":"2019","journal-title":"Andrologia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5162","DOI":"10.4049\/jimmunol.1001958","article-title":"Testosterone Replacement Effectively Inhibits the Development of Experimental Autoimmune Orchitis in Rats: Evidence for a Direct Role of Testosterone on Regulatory T Cell Expansion","volume":"186","author":"Fijak","year":"2011","journal-title":"J. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s00795-012-0587-2","article-title":"Experimental Autoimmune Orchitis as a Model of Immunological Male Infertility","volume":"45","author":"Naito","year":"2012","journal-title":"Med. Mol. Morphol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1093\/humupd\/dmy009","article-title":"Infectious, Inflammatory and \u2018Autoimmune\u2019 Male Factor Infertility: How Do Rodent Models Inform Clinical Practice?","volume":"24","author":"Fijak","year":"2018","journal-title":"Hum. Reprod. Update"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"583135","DOI":"10.3389\/fimmu.2020.583135","article-title":"Pathomechanisms of Autoimmune Based Testicular Inflammation","volume":"11","author":"Lustig","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s00441-022-03703-z","article-title":"Unraveling the Effect of the Inflammatory Microenvironment in Spermatogenesis Progression","volume":"392","author":"Ferreiro","year":"2023","journal-title":"Cell Tissue Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1002\/j.1939-4640.1994.tb00478.x","article-title":"Alterations of Testicular Function after Induced Autoimmune Orchitis in Rats","volume":"15","author":"Suescun","year":"1994","journal-title":"J. Androl."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Jarazo Dietrich, S., Fass, M.I., Jacobo, P.V., Sobarzo, C.M.A., Lustig, L., and Theas, M.S. (2015). Inhibition of NOS-NO System Prevents Autoimmune Orchitis Development in Rats: Relevance of NO Released by Testicular Macrophages in Germ Cell Apoptosis and Testosterone Secretion. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128709"},{"key":"ref_10","first-page":"1689","article-title":"Testicular Dysgenesis Does Not Affect Expression of Anti-M\u00fcllerian Hormone by Sertoli Cells in Premeiotic Seminiferous Tubules","volume":"148","author":"Rey","year":"1996","journal-title":"Am. J. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/BF00335713","article-title":"Quantitation of the Cells of the Seminiferous Epithelium of the Human Testis Employing the Sertoli Cell as a Constant","volume":"115","author":"Rowley","year":"1971","journal-title":"Z. Zellforsch."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"626","DOI":"10.2307\/3570998","article-title":"Damage and Recovery of Mouse Testis after 1000 r Acute Localized X-Irradiation, with Reference to Restitution Cells, Sertoli Cell Increase, and Type A Spermatogonial Recovery","volume":"12","author":"Nebel","year":"1960","journal-title":"Radiat. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1093\/humrep\/del279","article-title":"Histological Evaluation of the Human Testis\u2014Approaches to Optimizing the Clinical Value of the Assessment: Mini Review","volume":"22","author":"McLachlan","year":"2007","journal-title":"Hum. Reprod."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1083\/jcb.84.2.340","article-title":"Morphometric Analysis of Leydig Cells in the Normal Rat Testis","volume":"84","author":"Mori","year":"1980","journal-title":"J. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1046\/j.1365-2605.1998.00076.x","article-title":"Increased Testosterone Production in Vitro by Leydig Cells from Rats with Severe Autoimmune Orchitis","volume":"20","author":"Suescun","year":"1998","journal-title":"Int. J. Androl."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/aja.2008.48","article-title":"The Reliability of Ultrasonographic Measurements for Testicular Volume Assessment: Comparison of Three Common Formulas with True Testicular Volume","volume":"11","author":"Hsieh","year":"2009","journal-title":"Asian J. Androl."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1095\/biolreprod.103.022822","article-title":"Bicarbonate Is Required for Migration of Sperm Epididymal Protein DE (CRISP-1) to the Equatorial Segment and Expression of Rat Sperm Fusion Ability","volume":"70","author":"Munuce","year":"2004","journal-title":"Biol. Reprod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1034\/j.1600-0897.2003.00074.x","article-title":"Germ Cell Apoptosis in Autoimmune Orchitis: Involvement of the Fas-FasL System","volume":"50","author":"Theas","year":"2003","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3430","DOI":"10.1242\/dev.150284","article-title":"Spermatogonial Kinetics in Humans","volume":"144","author":"Saracino","year":"2017","journal-title":"Development"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"211","DOI":"10.3109\/01913129609016317","article-title":"The Human Blood-Testis Barrier in Impaired Spermatogenesis","volume":"20","author":"Cavicchia","year":"1996","journal-title":"Ultrastruct. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"224","DOI":"10.3389\/fendo.2019.00224","article-title":"Molecular Mechanisms and Signaling Pathways Involved in Sertoli Cell Proliferation","volume":"10","author":"Meroni","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e13083","DOI":"10.1111\/and.13083","article-title":"Germ Cell Apoptosis and Survival in Testicular Inflammation","volume":"50","author":"Theas","year":"2018","journal-title":"Andrologia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e13481","DOI":"10.1111\/aji.13481","article-title":"Evaluation of Immune Status in Testis and Macrophage Polarization Associated with Testicular Damage in Patients with Nonobstructive Azoospermia","volume":"86","author":"Zheng","year":"2021","journal-title":"Am. J. Rep. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e536","DOI":"10.1111\/j.1365-2605.2010.01137.x","article-title":"Immunodeviation towards a Th17 Immune Response Associated with Testicular Damage in Azoospermic Men: Testicular Th17 Immune Response in Azoospermic Men","volume":"34","author":"Duan","year":"2011","journal-title":"Int. J. Androl."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/S0015-0282(02)03206-5","article-title":"Number, Distribution Pattern, and Identification of Macrophages in the Testes of Infertile Men","volume":"78","author":"Frungieri","year":"2002","journal-title":"Fertil. Steril."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e13055","DOI":"10.1111\/and.13055","article-title":"Human Testicular Peritubular Cells, Mast Cells and Testicular Inflammation","volume":"50","author":"Mayerhofer","year":"2018","journal-title":"Andrologia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1038\/modpathol.2011.97","article-title":"Reduced Numbers of Sertoli, Germ, and Spermatogonial Stem Cells in Impaired Spermatogenesis","volume":"24","author":"Hentrich","year":"2011","journal-title":"Mod. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/S0015-0282(97)00372-5","article-title":"In Situ End-Labeling of Human Testicular Tissue Demonstrates Increased Apoptosis in Conditions of Abnormal Spermatogenesis","volume":"68","author":"Lin","year":"1997","journal-title":"Fertil. Steril."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1093\/molehr\/4.3.227","article-title":"The Proliferation of Spermatogonia in Normal and Pathological Human Seminiferous Epithelium: An Immunohistochemical Study Using Monoclonal Antibodies against Ki-67 Protein and Proliferating Cell Nuclear Antigen","volume":"4","author":"Steger","year":"1998","journal-title":"Mol. Hum. Reprod."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"906381","DOI":"10.3389\/fendo.2022.906381","article-title":"AMH Regulation by Steroids in the Mammalian Testis: Underlying Mechanisms and Clinical Implications","volume":"13","author":"Edelsztein","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Lan, K.-C., Chen, Y.-T., Chang, C., Chang, Y.-C., Lin, H.-J., Huang, K.-E., and Kang, H.-Y. (2013). Up-Regulation of SOX9 in Sertoli Cells from Testiculopathic Patients Accounts for Increasing Anti-Mullerian Hormone Expression via Impaired Androgen Receptor Signaling. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076303"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3722","DOI":"10.1210\/en.2003-0379","article-title":"Thyroid Hormone, Retinoic Acid, and Testosterone Suppress Proliferation and Induce Markers of Differentiation in Cultured Rat Sertoli Cells","volume":"144","author":"Buzzard","year":"2003","journal-title":"Endocrinology"},{"key":"ref_33","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":"ref_34","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1080\/15384101.2016.1207835","article-title":"Sertoli Cells Are Capable of Proliferation into Adulthood in the Transition Region between the Seminiferous Tubules and the Rete Testis in Wistar Rats","volume":"15","author":"Figueiredo","year":"2016","journal-title":"Cell Cycle"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.diff.2021.06.002","article-title":"Insights into Differentiation and Function of the Transition Region between the Seminiferous Tubule and Rete Testis","volume":"120","author":"Figueiredo","year":"2021","journal-title":"Differentiation"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1002\/stem.2065","article-title":"A Niche for GFR\u03b11-Positive Spermatogonia in the Terminal Segments of the Seminiferous Tubules in Hamster Testes","volume":"33","author":"Aiyama","year":"2015","journal-title":"Stem Cells"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jri.2003.10.003","article-title":"Endotoxin and Proinflammatory Cytokines Modulate Sertoli Cell Proliferation in Vitro","volume":"61","author":"Petersen","year":"2004","journal-title":"J. Reprod. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0303-7207(01)00680-3","article-title":"Interleukin-1 Is a Potent Growth Factor for Immature Rat Sertoli Cells","volume":"186","author":"Petersen","year":"2002","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/and.12026","article-title":"Histological and Hormonal Testicular Function in Oligo\/Azoospermic Infertile Men","volume":"45","author":"Lardone","year":"2013","journal-title":"Andrologia"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e13636","DOI":"10.1111\/and.13636","article-title":"Evaluation of Blood\u2013Testis Barrier Integrity in Terms of Adhesion Molecules in Nonobstructive Azoospermia","volume":"52","author":"Aydin","year":"2020","journal-title":"Andrologia"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1172\/JCI89927","article-title":"Egress of Sperm Autoantigen from Seminiferous Tubules Maintains Systemic Tolerance","volume":"127","author":"Tung","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e13092","DOI":"10.1111\/and.13092","article-title":"The Role of Regulatory T Cells in Autoimmune Orchitis","volume":"50","author":"Jacobo","year":"2018","journal-title":"Andrologia"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1095\/biolreprod.103.021329","article-title":"Nitric Oxide\/Nitric Oxide Synthase, Spermatogenesis, and Tight Junction Dynamics1","volume":"70","author":"Lee","year":"2004","journal-title":"Biol. Reprod."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Stammler, A., L\u00fcftner, B.U., Kliesch, S., Weidner, W., Bergmann, M., Middendorff, R., and Konrad, L. (2016). Highly Conserved Testicular Localization of Claudin-11 in Normal and Impaired Spermatogenesis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0160349"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.semcdb.2021.04.007","article-title":"Therapeutic Application of Sertoli Cells for Treatment of Various Diseases","volume":"121","author":"Washburn","year":"2022","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_46","first-page":"280","article-title":"F127 (or p407) poloxamer as a promising gelling agent in Sertoli cell delivery for cell therapy of the testis","volume":"79","author":"Jacobo","year":"2019","journal-title":"Rev. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"121251","DOI":"10.1016\/j.lfs.2022.121251","article-title":"The Potential of Sertoli Cells (SCs) Derived Exosomes and Its Therapeutic Efficacy in Male Reproductive Disorders","volume":"312","author":"Amiri","year":"2023","journal-title":"Life Sci."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/13\/4\/278\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:30:45Z","timestamp":1760106645000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/13\/4\/278"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,19]]},"references-count":47,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["biology13040278"],"URL":"https:\/\/doi.org\/10.3390\/biology13040278","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,19]]}}}