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JNK signalling is evolutionarily conserved and involved in multiple critical biological processes. Here, we found that the double knockout of <jats:italic>Jnk1<\/jats:italic> and <jats:italic>Jnk2<\/jats:italic> resulted in aberrant localisation of Sertoli cells at early developmental stages, with most Sertoli cells being lost at later stages. Further studies revealed that the inactivation of JNK signalling caused polarity loss in Sertoli cells. In vitro\u2010cultured <jats:italic>Jnk1\/2\u2010DKO<\/jats:italic> Sertoli cells exhibited a senescence\u2010associated phenotype. Mechanistic studies demonstrate that JNK signalling is likely involved in establishing Sertoli cell polarity by regulating the expression of TGF\u2010\u03b22, mediated by <jats:italic>c\u2010Jun<\/jats:italic>. The senescence of Sertoli cells in JNKs\u2010deficient mice is caused by aberrant proteolysis of P27<jats:sup>KIP1<\/jats:sup>, mediated by <jats:italic>c\u2010Myc<\/jats:italic>. This study demonstrates the role of JNK signalling in Sertoli cell development and functional maintenance, which may also represent an aetiology of male infertility in humans.<\/jats:p>","DOI":"10.1111\/cpr.13760","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T12:15:33Z","timestamp":1727439333000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Inactivation of <scp>JNK<\/scp> signalling results in polarity loss and cell senescence of Sertoli cell"],"prefix":"10.1111","volume":"58","author":[{"given":"Zhiming","family":"Shen","sequence":"first","affiliation":[{"name":"Guangdong Cardiovascular Institute Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences  Guangzhou China"},{"name":"Department of Reproductive Medicine Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University  Guangzhou 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