{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T03:20:19Z","timestamp":1789788019465,"version":"4.0.1"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T00:00:00Z","timestamp":1733443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      To address knowledge gaps, this study aimed to investigate the involvement of inflammasomes in the etiology of azoospermia. This study focused on the gene expression of key inflammasome components, including\n                      <jats:italic>NLR family pyrin domain containing 3 (NLRP-3), CASPASE-1, Interleukin-1\u03b2 (IL-1\u03b2), Interleukin-18 (IL-18), NLR family CARD domain-containing protein 4\/ice protease-activating factor (NLRC-4\/IPAF)<\/jats:italic>\n                      , and\n                      <jats:italic>Absent in melanoma 2 (AIM-2)<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed gene expression in blood and testicular tissue from patients with obstructive azoospermia (OA) and non-obstructive azoospermia (NOA). Additionally, we compared IL-1\u03b2 and IL-18 expression levels in seminal plasma samples using the Enzyme-Linked Immunosorbent Assay (ELISA) method. For comparison, blood samples from normospermic (NS) individuals were also genetically evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our results indicated significantly higher gene expression of inflammasome components in NOA patients than those in OA patients either in blood or in testicular tissue. Both azoospermic groups exhibited higher mRNA levels of inflammasome genes comparing with those from blood samples of NS men. Seminal plasma samples showed significantly increased levels of IL-1\u03b2 and IL-18 in NOA patients compared to men with OA. The ROC curve analysis indicated strong and significant predictive power of\n                      <jats:italic>IL-18, AIM-2<\/jats:italic>\n                      and\n                      <jats:italic>NLRC-4\/IPAF<\/jats:italic>\n                      gene expression profiles between NOA vs. NS patients and NOA vs. OA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings highlight the role of hidden chronic inflammation in azoospermia, particularly within the NOA group. This study provides a foundation for further detailed research, which could aid in the development of diagnostic panels to differentiate between various azoospermic groups.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2024.1507885","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T00:10:30Z","timestamp":1733443830000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["The role of inflammasome dysregulation in obstructive and non-obstructive azoospermia: a comparative molecular analysis of blood, tissue, and seminal plasma"],"prefix":"10.3389","volume":"15","author":[{"given":"Seyyed AmirHossein","family":"Mirghanizadeh Bafghi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzaneh","family":"Fesahat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fateme","family":"Zare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Imani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serajoddin","family":"Vahidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein","family":"Ansariniya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"ZareHoroki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein","family":"Hadinedoushan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.4161\/spmg.28218","article-title":"Review of azoospermia","volume":"4","author":"Wosnitzer","year":"2014","journal-title":"Spermatogenesis"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2022.05.011","article-title":"Genetic architecture of azoospermia\u2014time to advance the standard of care","volume":"83","author":"Wyrwoll","year":"2023","journal-title":"Eur Urol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"3267","DOI":"10.21037\/tau-21-320","article-title":"The expression of Beclin-1 in testicular tissues of non-obstructive azoospermia patients and its predictive value in sperm retrieval rate","volume":"10","author":"Zhou","year":"2021","journal-title":"Trans Androl Urol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"15","DOI":"10.6061\/clinics\/2013(Sup01)03","article-title":"The epidemiology and etiology of azoospermia","volume":"68","author":"Cocuzza","year":"2013","journal-title":"Clinics"},{"key":"B5","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1111\/iju.15301","article-title":"Clinical management of nonobstructive azoospermia: An update","volume":"31","author":"Takeshima","year":"2024","journal-title":"Int J Urol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/aji.2013.70.issue-6","article-title":"The gene expression analysis of paracrine\/autocrine factors in patients with spermatogenetic failure compared with normal spermatogenesis","volume":"70","author":"Malcher","year":"2013","journal-title":"Am J Reprod Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.3390\/jcm10071400","article-title":"Reproductive chances of men with azoospermia due to spermatogenic dysfunction","volume":"10","author":"Kang","year":"2021","journal-title":"J Clin Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s12610-022-00157-9","article-title":"The NLRP3 inflammasome: molecular activation and regulation in spermatogenesis and male infertility; a systematic review","volume":"32","author":"Tavalaee","year":"2022","journal-title":"Basic Clin Androl"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.729539","article-title":"Varicocele-mediated male infertility: from the perspective of testicular immunity and inflammation","volume":"12","author":"Fang","year":"2021","journal-title":"Front Immunol"},{"key":"B10","article-title":"Impact of varicocele and varicocelectomy on the apoptosis of spermatogenic cells and the levels of nitrogen monoxidum and interleukin 1 in the rat testis","volume":"22","author":"Xu","year":"2016","journal-title":"Zhonghua Nan Ke Xue"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e13734","DOI":"10.1111\/aji.13734","article-title":"Insight toward inflammasome complex contribution to male infertility","volume":"90","author":"Minas","year":"2023","journal-title":"Am J Reprod Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1530\/REP-18-0111","article-title":"NLRP3 in somatic non-immune cells of rodent and primate testes","volume":"156","author":"Walenta","year":"2018","journal-title":"Reproduction"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/nature07725","article-title":"AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC","volume":"458","author":"Hornung","year":"2009","journal-title":"Nature"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.08.016","article-title":"IPAF inflammasome is involved in interleukin-1\u03b2 production from astrocytes, induced by palmitate; implications for Alzheimer\u2019s disease","volume":"35","author":"Liu","year":"2014","journal-title":"Neurobiol Aging"},{"key":"B15","doi-asserted-by":"publisher","first-page":"gaad035","DOI":"10.1093\/molehr\/gaad035","article-title":"Inflammasomes in human reproductive diseases","volume":"29","author":"Chen","year":"2023","journal-title":"Mol Hum Reprod"},{"key":"B16","doi-asserted-by":"publisher","first-page":"490","DOI":"10.37349\/ei","article-title":"Research progress on NLRP3 inflammasomes in male reproductive immunity","volume":"4","author":"Zhang","year":"2024","journal-title":"Explor Immunol."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2013.80","article-title":"dsDNA ASCs for caspase 8-mediated apoptosis","volume":"20","author":"Grabinger","year":"2013","journal-title":"Cell Death Differ"},{"key":"B18","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1093\/humupd\/dmh003","article-title":"Role of caspases in male infertility","volume":"10","author":"Said","year":"2004","journal-title":"Hum Reprod Update"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e20190314","DOI":"10.1084\/jem.20190314","article-title":"Inflammasome signaling and regulation of interleukin-1 family cytokines","volume":"217","author":"Chan","year":"2019","journal-title":"J Exp Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2013.12.005","article-title":"IL-18 levels in the semen of male infertility: semen analysis","volume":"64","author":"Qian","year":"2014","journal-title":"Int J Biol Macromol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"493","DOI":"10.18502\/ijrm.v19i6.9371","article-title":"Role of sperm apoptosis and oxidative stress in male infertility: A narrative review","volume":"19","author":"Asadi","year":"2021","journal-title":"Int J Reprod Biomed"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e14556","DOI":"10.1111\/and.14556","article-title":"ANXA2, SP17, SERPINA5, PRDX2 genes, and sperm DNA fragmentation differentially represented in male partners of infertile couples with normal and abnormal sperm parameters","volume":"54","author":"Afsari","year":"2022","journal-title":"Andrologia"},{"key":"B23","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1038\/s41421-020-0167-x","article-title":"Inflammasome activation and regulation: toward a better understanding of complex mechanisms","volume":"6","author":"Zheng","year":"2020","journal-title":"Cell Discov"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00670-3","article-title":"An update on the regulatory mechanisms of NLRP3 inflammasome activation","volume":"18","author":"Paik","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.fertnstert.2012.09.004","article-title":"Involvement of the inflammasome in abnormal semen quality of men with spinal cord injury","volume":"99","author":"Zhang","year":"2013","journal-title":"Fertil Steril"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.55730\/1300-0144.5631","article-title":"What is the impact of inflammasome mechanisms on male infertility","volume":"53","author":"\u00d6rdek","year":"2023","journal-title":"Turkish J Med Sci"},{"key":"B27","doi-asserted-by":"publisher","first-page":"e14572","DOI":"10.1111\/and.v54.11","article-title":"Do inflammatory markers such as NLRP3 and IL1-\u03b2 have an effect on the prediction of testicular sperm extraction success in infertile men","volume":"54","author":"Kati","year":"2022","journal-title":"Andrologia"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1021\/es402025n","article-title":"Urinary metabolic biomarkers link oxidative stress indicators associated with general arsenic exposure to male infertility in a Han Chinese population","volume":"47","author":"Shen","year":"2013","journal-title":"Environ Sci Technol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0232357","article-title":"Hypoxia-related long noncoding RNAs are associated with varicocele-related male infertility","volume":"15","author":"Ata-Abadi","year":"2020","journal-title":"PloS One"},{"key":"B30","doi-asserted-by":"publisher","first-page":"96","DOI":"10.2478\/enr-2020-0012","article-title":"Involvement of Asc and Nlrp3 inflammasomes in the testes following spinal cord injury","volume":"54","author":"Ramezanikhah","year":"2020","journal-title":"Endocrine Regulat"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s43032-020-00253-z","article-title":"Immunoendocrine markers of stress in seminal plasma at IVF\/ICSI failure: a preliminary study","volume":"28","author":"Nikolaeva","year":"2021","journal-title":"Reprod Sci"},{"key":"B32","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.jri.2016.03.006","article-title":"The relationship of seminal transforming growth factor-\u03b21 and interleukin-18 with reproductive success in women exposed to seminal plasma during IVF\/ICSI treatment","volume":"117","author":"Nikolaeva","year":"2016","journal-title":"J Reprod Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvab202","article-title":"AIM2-driven inflammasome activation in heart failure","volume":"117","author":"On\u00f3di","year":"2021","journal-title":"Cardiovasc Res"},{"key":"B34","doi-asserted-by":"publisher","first-page":"7895","DOI":"10.1038\/s41598-019-44261-9","article-title":"Upregulation of the NLRC4 inflammasome contributes to poor prognosis in glioma patients","volume":"9","author":"Lim","year":"2019","journal-title":"Sci Rep"},{"key":"B35","doi-asserted-by":"publisher","first-page":"55","DOI":"10.21037\/atm-22-5601","article-title":"Identification of biomarkers associated with macrophage infiltration in non-obstructive azoospermia using single-cell transcriptomic and microarray data","volume":"11","author":"Luo","year":"2023","journal-title":"Ann Trans Med"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.21037\/tau-23-130","article-title":"Proteomic approach towards identification of seminal fluid biomarkers from individuals with severe oligozoospermia, cryptozoospermia and non-obstructive azoospermia: a pilot study","volume":"12","author":"Nowicka-Bauer","year":"2023","journal-title":"Trans Androl Urol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"3264","DOI":"10.3390\/ijms22063264","article-title":"Genetics of azoospermia","volume":"22","author":"Cioppi","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B38","doi-asserted-by":"publisher","first-page":"3328","DOI":"10.3390\/ijms20133328","article-title":"The NLRP3 inflammasome: an overview of mechanisms of activation and regulation","volume":"20","author":"Kelley","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1038\/s12276-024-01261-8","article-title":"NLRP3 inflammasome: a key player in the pathogenesis of life-style disorders","volume":"56","author":"Ramachandran","year":"2024","journal-title":"Exp Mol Med"},{"key":"B40","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s11481-024-10101-5","article-title":"New insights on NLRP3 inflammasome: mechanisms of activation, inhibition, and epigenetic regulation","volume":"19","author":"kodi","year":"2024","journal-title":"J Neuroimmune Pharmacol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"872","DOI":"10.3390\/ijms22020872","article-title":"Structure, activation and regulation of NLRP3 and AIM2 inflammasomes","volume":"22","author":"Sharma","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1111\/andr.13568","article-title":"Reproductive and obstetric outcomes in TESE\u2013ICSI cycles: A comparison between obstructive and non-obstructive azoospermia","volume":"18","author":"Romano","year":"2023","journal-title":"Andrology"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.4103\/jhrs.JHRS_41_19","article-title":"Comparative analysis of surgically retrieved sperms in cases of obstructive and nonobstructive azoospermia treated for infertility","volume":"13","author":"Talreja","year":"2020","journal-title":"J Hum Reprod Sci"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1139450","article-title":"Microbiology and immune mechanisms associated with male infertility","volume":"14","author":"Chen","year":"2023","journal-title":"Front Immunol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.4103\/aja202488","article-title":"Research advances in inflammation and oxidative stress in varicocele-induced male infertility: a narrative review","volume":"11","author":"Wang","year":"2024","journal-title":"Asian J Androl"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.3390\/jpm13091362","article-title":"Evaluating the predictive value of diagnostic testicular biopsy for sperm retrieval outcomes in men with non-obstructive azoospermia","volume":"13","author":"Kaltsas","year":"2023","journal-title":"J Pers Med"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.v80.11","article-title":"Clinical characteristics and treatment of azoospermia and severe oligospermia patients with Y-chromosome microdeletions","volume":"80","author":"Zhang","year":"2013","journal-title":"Mol Reprod Dev"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.androl.2019.09.005","article-title":"Evaluation of depression, anxiety and quality of life in patients with non-obstructive azoospermia","volume":"19","author":"Topuz","year":"2021","journal-title":"Rev Internacional Androlog\u00eda"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1507885\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T00:10:33Z","timestamp":1733443833000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1507885\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,6]]},"references-count":48,"alternative-id":["10.3389\/fimmu.2024.1507885"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1507885","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,6]]},"article-number":"1507885"}}