{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lei H"],"funding":["MOST | Dream Project of Ministry of Science and Technology of the People's Republic of China (Dream Project of MOST of China)"],"pagination":["e2514837122"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12377765"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["122(33)"],"pubmed_abstract":["Male infertility remains a major unmet medical challenge, with poorly defined molecular mechanisms and no effective therapies. Here, we identify a stress granule-mediated necroptotic pathway as a key driver of non-obstructive azoospermia, a severe form of male infertility marked by the loss of spermatogenesis. Environmental or physiological stress activates eIF2α kinases, inducing stress granule formation and the recruitment of ZBP1 and RIPK3 into a cytoplasmic complex. This assembly triggers RIPK3 activation, MLKL phosphorylation, and necroptotic death of spermatogonia and Sertoli cells. Genetic ablation of <i>Zbp1</i> or <i>Ripk3</i> protects mice from heat-induced testicular degeneration, establishing their essential role in stress-induced testicular damage. Importantly, activation of t"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Stress granule-mediated ZBP1 activation drives necroptotic cell death in non-obstructive azoospermia and testicular aging."],"pmcid":["PMC12377765"],"funding_grant_id":["n/a"],"pubmed_authors":["Jiang K","Fan W","Tian L","Du B","Li D","Chen J","Lei H","Xu T","Han H","Wang X"],"additional_accession":[]},"is_claimable":false,"name":"Stress granule-mediated ZBP1 activation drives necroptotic cell death in non-obstructive azoospermia and testicular aging.","description":"Male infertility remains a major unmet medical challenge, with poorly defined molecular mechanisms and no effective therapies. Here, we identify a stress granule-mediated necroptotic pathway as a key driver of non-obstructive azoospermia, a severe form of male infertility marked by the loss of spermatogenesis. Environmental or physiological stress activates eIF2α kinases, inducing stress granule formation and the recruitment of ZBP1 and RIPK3 into a cytoplasmic complex. This assembly triggers RIPK3 activation, MLKL phosphorylation, and necroptotic death of spermatogonia and Sertoli cells. Genetic ablation of <i>Zbp1</i> or <i>Ripk3</i> protects mice from heat-induced testicular degeneration, establishing their essential role in stress-induced testicular damage. Importantly, activation of t","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-05-10T01:51:30.169Z","creation":"2026-04-08T01:25:43.042Z"},"accession":"S-EPMC12377765","cross_references":{"pubmed":["40811463"],"doi":["10.1073/pnas.2514837122"]}}