{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T12:24:35Z","timestamp":1787228675747,"version":"build-2736575974"},"reference-count":54,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82574057"],"award-info":[{"award-number":["82574057"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073520"],"award-info":[{"award-number":["82073520"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Nanoplastics (NPs), owing to their small size and ability to cross the blood\u2013testis barrier, pose a potential risk to the male reproductive system. However, the molecular mechanisms underlying NP\u2010induced reproductive toxicity, particularly cell senescence, remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      This study aims to investigate the mechanisms by which polystyrene nanoplastics (PS\u2010NPs) induce spermatocyte senescence, with a particular focus on the role of YTHDF3\u2010mediated m\n                      <jats:sup>6<\/jats:sup>\n                      A RNA methylation in regulating the cGAS\u2010NF\u2010\u03baB signaling pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Exposure was established in male C57BL\/6 mice via tracheal instillation of PS\u2010NPs, supplemented with spermatogonial cells (GC\u20102). Testicular dysfunction and spermatocyte senescence were assessed. Further investigations focused on m\n                      <jats:sup>6<\/jats:sup>\n                      A modification and the cGAS\u2010NF\u2010\u03baB signaling axis. Functional studies and knockout experiments were conducted to investigate the role of YTHDF3 and its phase separation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PS\u2010NPs exposure led to disrupted testicular architecture, decreased sperm quality, and induced spermatocyte senescence in a concentration\u2010dependent manner. Mechanistically, PS\u2010NPs activated the cGAS\u2010NF\u2010\u03baB signaling axis, resulting in reduced mitochondrial membrane potential and impaired mitochondrial function. This activation not only promoted senescence but also suppressed antioxidant defenses, accelerating the aging process. Epigenetically, PS\u2010NPs upregulated the m\n                      <jats:sup>6<\/jats:sup>\n                      A methyltransferase METTL3 and the reader protein YTHDF3. YTHDF3 underwent liquid\u2013liquid phase separation (LLPS) to form intracellular condensates, directly binding to m\n                      <jats:sup>6<\/jats:sup>\n                      A\u2010modified sites on cGAS mRNA and regulating its stability. Knockdown of YTHDF3 significantly attenuated cGAS activation and alleviated the senescence phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion and Conclusion<\/jats:title>\n                    <jats:p>\n                      This study identifies a novel mechanism where YTHDF3\u2010mediated m\n                      <jats:sup>6<\/jats:sup>\n                      A modification, driven by phase separation, activates the cGAS\u2010NF\u2010\u03baB pathway in response to PS\u2010NPs, leading to mitochondrial damage and spermatocyte senescence. These findings provide new insights into the epigenetic and phase separation\u2010based mechanisms of nanoplastic reproductive toxicity and suggest potential intervention strategies targeting m\n                      <jats:sup>6<\/jats:sup>\n                      A modification, phase separation, or the cGAS pathway.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70357","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T11:33:00Z","timestamp":1787225580000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["YTHDF3\u2010Dependent m\n                    <sup>6<\/sup>\n                    A Modification of cGAS Drives Nanoparticle\u2010Induced Senescence in Spermatocytes"],"prefix":"10.1111","author":[{"given":"Jiayi","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Occupational Health and Environmental Health School of Public Health Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Occupational Health and Environmental Health School of Public Health Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiwen","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Occupational Health and Environmental Health School of Public Health Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Occupational Health and Environmental Health School of Public Health Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Occupational 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