{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:48:06Z","timestamp":1790052486531,"version":"4.0.1"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"33","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012503","name":"MOST | Dream Project of Ministry of Science and Technology of the People\u2018s Republic of China","doi-asserted-by":"publisher","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/501100012503","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,8,19]]},"abstract":"<jats:p>\n                    Male infertility remains a major unmet medical challenge, with poorly defined molecular mechanisms and no effective therapies. Here, we identify a stress granule\u2013mediated 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 eIF2\u03b1 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\n                    <jats:italic toggle=\"yes\">Zbp1<\/jats:italic>\n                    or\n                    <jats:italic toggle=\"yes\">Ripk3<\/jats:italic>\n                    protects mice from heat-induced testicular degeneration, establishing their essential role in stress-induced testicular damage. Importantly, activation of this pathway is also observed in aged human testes, linking stress-responsive necroptosis to both pathological infertility and the broader process of reproductive aging. These findings reveal an unrecognized mechanism that couples cellular stress responses to regulated cell death in the male reproductive system.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2514837122","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T17:51:32Z","timestamp":1755193892000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":13,"title":["Stress granule\u2013mediated ZBP1 activation drives necroptotic cell death in non-obstructive azoospermia and testicular aging"],"prefix":"10.1073","volume":"122","author":[{"given":"Hongen","family":"Lei","sequence":"first","affiliation":[{"name":"Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"Institute of Urology, Capital Medical University","place":["Beijing, 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