{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:42:43Z","timestamp":1791895363308,"version":"4.3.4"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"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":[[2026,7]]},"abstract":"<jats:p>Human spermatogonial stem cells (SSCs) are crucial for spermatogenesis and male reproduction. Although abnormal pyroptosis caused by inflammation impacts male fertility, the molecular mechanisms underlying the pyroptosis of human SSCs are elusive. To induce pyroptosis, lipopolysaccharide (LPS) was introduced into the vas deferens of mice. RNA sequencing (RNA-Seq) of human SSCs was employed to identify NOD-like receptor thermal protein domain associated protein 3 (NLRP3), and RNA interference (RNAi) was used to determine the function and mechanism of NLRP3 in controlling pyroptosis of human SSCs. Guanylate-binding protein 4 (GBP4) was analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein\u2013protein interaction (PPI) analyses, and the impact of GBP4 on NLRP3 in human SSCs was subsequently assessed using GBP4 short hairpin RNA (shRNA). LPS reduced the testicular weight of mice, disrupted spermatogenesis, and increased the levels of inflammatory factors (interleukin-18 [IL-18] and interleukin-1\u03b2 [IL-1\u03b2]). NLRP3 siRNAs antagonized the LPS-induced increases in IL-18 and IL-1\u03b2, proliferative inhibition, and pyroptosis (Caspase 1 and Gasdermin D) in human SSCs. An association between GBP4 and NLRP3 in human SSCs was identified by co-immunoprecipitation (Co-IP). Human SSCs with stable GBP4 shRNA decreased the expression level of NLRP3 in human SSCs under inflammatory conditions. Collectively, these results imply that LPS-induced NLRP3 activation enhances the pyroptosis of human SSCs via the regulation of GBP4. This study offers novel insights into molecular mechanisms underlying the fate determinations of human SSCs.<\/jats:p>","DOI":"10.4103\/aja202564","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T06:00:09Z","timestamp":1768802409000},"page":"416-426","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["NLRP3 activation by lipopolysaccharide (LPS) mediates the pyroptosis of human spermatogonial stem cells via GBP4 regulation"],"prefix":"10.4103","volume":"28","author":[{"given":"Wen-Cong","family":"Jin","sequence":"first","affiliation":[{"name":"Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University School of Basic Medicine, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University School of Basic Medicine, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Hong","family":"Cui","sequence":"additional","affiliation":[{"name":"Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University School of Basic Medicine, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Du","sequence":"additional","affiliation":[{"name":"Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University School of Basic Medicine, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuping","family":"He","sequence":"additional","affiliation":[{"name":"Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University School of Basic Medicine, Changsha 410013, China"},{"name":"Key Laboratory of Reproductive Health Diseases Research and Translation, Ministry of Education, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"R1-20260702","first-page":"208","article-title":"WHO manual for the standardized investigation, diagnosis and management of the infertile male","volume":"1","author":"Niederberger","year":"2000","journal-title":"Urology"},{"key":"R2-20260702","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1148\/rg.2017160125","article-title":"Role of imaging in the evaluation of male infertility","volume":"37","author":"Mittal","year":"2017","journal-title":"Radiographics"},{"key":"R3-20260702","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.repbio.2019.07.005","article-title":"Diet and sperm quality: nutrients, foods and dietary patterns","volume":"19","author":"Salas-Huetos","year":"2019","journal-title":"Reprod Biol"},{"key":"R4-20260702","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1007\/s00345-013-1082-7","article-title":"Male urogenital infections: impact of infection and inflammation on ejaculate parameters","volume":"31","author":"Weidner","year":"2013","journal-title":"World J Urol"},{"key":"R6-20260702","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nrmicro2070","article-title":"Pyroptosis: host cell death and inflammation","volume":"7","author":"Bergsbaken","year":"2009","journal-title":"Nat Rev Microbiol"},{"key":"R7-20260702","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.mib.2013.04.004","article-title":"Inflammasome-mediated pyroptotic and apoptotic cell death, and defense against infection","volume":"16","author":"Aachoui","year":"2013","journal-title":"Curr Opin Microbiol"},{"key":"R8-20260702","doi-asserted-by":"crossref","first-page":"5113","DOI":"10.4049\/jimmunol.1202479","article-title":"Cutting edge: nitric oxide inhibits the NLRP3 inflammasome","volume":"189","author":"Hernandez-Cuellar","year":"2012","journal-title":"J Immunol"},{"key":"R9-20260702","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.neubiorev.2018.02.005","article-title":"ATP-activated P2X7 receptor in the pathophysiology of mood disorders and as an emerging target for the development of novel antidepressant therapeutics","volume":"87","author":"Wei","year":"2018","journal-title":"Neurosci Biobehav Rev"},{"key":"R10-20260702","doi-asserted-by":"crossref","first-page":"aag2045","DOI":"10.1126\/sciimmunol.aag2045","article-title":"ZBP1\/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways","volume":"1","author":"Kuriakose","year":"2016","journal-title":"Sci Immunol"},{"key":"R11-20260702","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1126\/science.aaf3036","article-title":"An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells","volume":"352","author":"Zanoni","year":"2016","journal-title":"Science"},{"key":"R12-20260702","doi-asserted-by":"crossref","first-page":"581165","DOI":"10.3389\/fimmu.2020.581165","article-title":"Bacterial outer membrane vesicle-mediated cytosolic delivery of flagellin triggers host NLRC4 canonical inflammasome signaling","volume":"11","author":"Yang","year":"2020","journal-title":"Front Immunol"},{"key":"R13-20260702","doi-asserted-by":"crossref","first-page":"100924","DOI":"10.1016\/j.mam.2020.100924","article-title":"An overview of the non-canonical inflammasome","volume":"76","author":"Downs","year":"2020","journal-title":"Mol Aspects Med"},{"key":"R14-20260702","doi-asserted-by":"crossref","first-page":"101182","DOI":"10.1016\/j.plipres.2022.101182","article-title":"Lipid-protein interactions regulating the canonical and the non-canonical NLRP3 inflammasome","volume":"87","author":"Pizzuto","year":"2022","journal-title":"Prog Lipid Res"},{"key":"R15-20260702","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.omtn.2020.04.016","article-title":"Hsa-miR-1908-3p mediates the self-renewal and apoptosis of human spermatogonial stem cells via targeting KLF2","volume":"20","author":"Chen","year":"2020","journal-title":"Mol Ther Nucleic Acids"},{"key":"R16-20260702","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s00018-024-05414-w","article-title":"LncRNA ACVR2B-as1 interacts with ALDOA to regulate the self-renewal and apoptosis of human spermatogonial stem cells by controlling glycolysis activity","volume":"81","author":"Xu","year":"2024","journal-title":"Cell Mol Life Sci"},{"key":"R17-20260702","first-page":"0544","article-title":"Essential regulation of YAP1 in fate determinations of spermatogonial stem cells and male fertility by interacting with RAD21 and targeting NEDD4 in humans and mice","volume":"7","author":"Li","year":"2024","journal-title":"Research (Wash D C)"},{"key":"R18-20260702","first-page":"0647","article-title":"Essential regulation of spermatogonial stem cell fate decisions and male fertility by APBB1 via interaction with KAT5 and GDF15 in humans and mice","volume":"8","author":"Zhou","year":"2025","journal-title":"Research (Wash D C)"},{"key":"R19-20260702","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.3390\/ijms22031319","article-title":"NLRP3 inflammasome: a new pharmacological target for reducing testicular damage associated with varicocele","volume":"22","author":"Antonuccio","year":"2021","journal-title":"Int J Mol Sci"},{"key":"R20-20260702","doi-asserted-by":"crossref","first-page":"8879","DOI":"10.18632\/oncotarget.7092","article-title":"Generation of functional hepatocytes from human spermatogonial stem cells","volume":"7","author":"Chen","year":"2016","journal-title":"Oncotarget"},{"key":"R22-20260702","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1136\/bmj.1.6121.1177","article-title":"Pituitary-testicular interrelationships in mumps orchitis and other viral infections","volume":"1","author":"Adamopoulos","year":"1978","journal-title":"Br Med J"},{"key":"R23-20260702","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1111\/j.1365-2605.2005.00499.x","article-title":"A neglected gland: a review of Cowper's gland","volume":"28","author":"Chughtai","year":"2005","journal-title":"Int J Androl"},{"key":"R24-20260702","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1038\/sj.cdd.4402194","article-title":"The pyroptosome: a supramolecular assembly of ASC dimers mediating inflammatory cell death via caspase-1 activation","volume":"14","author":"Fernandes-Alnemri","year":"2007","journal-title":"Cell Death Differ"},{"key":"R25-20260702","doi-asserted-by":"crossref","first-page":"11570","DOI":"10.1074\/jbc.M112208200","article-title":"PYPAF1, a PYRIN-containing Apaf1-like protein that assembles with ASC and regulates activation of NF-kappa B","volume":"277","author":"Manji","year":"2002","journal-title":"J Biol Chem"},{"key":"R26-20260702","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/j.1600-065X.2008.00734.x","article-title":"Function of Nod-like receptors in microbial recognition and host defense","volume":"227","author":"Franchi","year":"2009","journal-title":"Immunol Rev"},{"key":"R27-20260702","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S1097-2765(02)00599-3","article-title":"The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta","volume":"10","author":"Martinon","year":"2002","journal-title":"Mol Cell"},{"key":"R28-20260702","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1111\/j.1462-5822.2006.00751.x","article-title":"Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages","volume":"8","author":"Fink","year":"2006","journal-title":"Cell Microbiol"},{"key":"R29-20260702","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/nature15514","article-title":"Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death","volume":"526","author":"Shi","year":"2015","journal-title":"Nature"},{"key":"R30-20260702","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/nature15541","article-title":"Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling","volume":"526","author":"Kayagaki","year":"2015","journal-title":"Nature"},{"key":"R31-20260702","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1038\/cr.2015.139","article-title":"Gasdermin D is an executor of pyroptosis and required for interleukin-1\u03b2secretion","volume":"25","author":"He","year":"2015","journal-title":"Cell Res"},{"key":"R32-20260702","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1038\/ni.1960","article-title":"Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria","volume":"11","author":"Miao","year":"2010","journal-title":"Nat Immunol"},{"key":"R33-20260702","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.immuni.2009.02.006","article-title":"The intracellular sensor NLRP3 mediates key innate and healing responses to influenza A virus via the regulation of caspase-1","volume":"30","author":"Thomas","year":"2009","journal-title":"Immunity"},{"key":"R34-20260702","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.immuni.2009.02.005","article-title":"The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA","volume":"30","author":"Allen","year":"2009","journal-title":"Immunity"},{"key":"R35-20260702","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/nature07965","article-title":"Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence","volume":"459","author":"Gross","year":"2009","journal-title":"Nature"},{"key":"R36-20260702","doi-asserted-by":"crossref","first-page":"36560","DOI":"10.1074\/jbc.M607594200","article-title":"Critical role for Cryopyrin\/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA","volume":"281","author":"Kanneganti","year":"2006","journal-title":"J Biol Chem"},{"key":"R37-20260702","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-2249.2011.04440.x","article-title":"The NLRP3 inflammasome in health and disease: the good, the bad and the ugly","volume":"166","author":"Menu","year":"2011","journal-title":"Clin Exp Immunol"},{"key":"R38-20260702","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/nm.3893","article-title":"Inflammasomes: mechanism of action, role in disease, and therapeutics","volume":"21","author":"Guo","year":"2015","journal-title":"Nat Med"},{"key":"R39-20260702","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1074\/jbc.M608083200","article-title":"ATP activates a reactive oxygen species-dependent oxidative stress response and secretion of proinflammatory cytokines in macrophages","volume":"282","author":"Cruz","year":"2007","journal-title":"J Biol Chem"},{"key":"R40-20260702","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nature09663","article-title":"A role for mitochondria in NLRP3 inflammasome activation","volume":"469","author":"Zhou","year":"2011","journal-title":"Nature"},{"key":"R41-20260702","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s00432-024-05605-9","article-title":"Guanylate binding protein 4 shapes an inflamed tumor microenvironment and identifies immuno-hot tumors","volume":"150","author":"Zhou","year":"2024","journal-title":"J Cancer Res Clin Oncol"},{"key":"R42-20260702","doi-asserted-by":"crossref","first-page":"12077","DOI":"10.1038\/ncomms12077","article-title":"Neutrophils mediate Salmonella typhimurium clearance through the GBP4 inflammasome-dependent production of prostaglandins","volume":"7","author":"Tyrkalska","year":"2016","journal-title":"Nat Commun"}],"container-title":["Asian Journal of Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/aja202564","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T19:40:51Z","timestamp":1786650051000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/aja202564"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,16]]},"references-count":40,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.4103\/aja202564","relation":{},"ISSN":["1745-7262","1008-682X"],"issn-type":[{"value":"1745-7262","type":"print"},{"value":"1008-682X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,16]]},"assertion":[{"value":"2025-03-29","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-09","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}