{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:51:33Z","timestamp":1787313093988,"version":"build-2736575974"},"reference-count":76,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T00:00:00Z","timestamp":1694822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004482","name":"Kuwait University","doi-asserted-by":"publisher","award":["SRUL02\/13"],"award-info":[{"award-number":["SRUL02\/13"]}],"id":[{"id":"10.13039\/501100004482","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The male reproductive system requires the pleiotropic activity of JAK\/STAT to maintain its function, especially spermatogenesis. The study aims to investigate the effect of JAK2 signaling on the expression of the Keap1\/Nrf2 axis, spermatogenesis, and the Sertoli cells (Sc) junctions in an animal model of testicular ischemia reperfusion injury (tIRI). Testes subjected to tIRI exhibited increased JAK2\/STAT3 activity associated with spermatogenic arrest and reduced expression of the Sc junctions. In addition, there was an increased protein expression of Keap1 and decreased Nrf2., which was coupled with the downregulation of gene expression of antioxidant enzymes. Reduced SOD and CAT activities were accompanied by increased lipid peroxidation and protein carbonylation during tIRI. Increased caspase 9 activity and Bax\/Bcl2 ratio indicated initiation of apoptosis. Inhibition of JAK2 activity by AG490 maintained the integrity of spermatogenesis and SC junctions, normalized the expression of the Keap1\/Nrf2 axis and its downstream antioxidant enzymes, and prevented germ cell apoptosis. The results further emphasized the regulatory role of JAK2\/STAT3 on spermatogenesis, Keap1\/Nrf2 signaling, and maintenance of the testicular redox balance to combat testicular dysfunction and male infertility.<\/jats:p>","DOI":"10.3390\/cells12182292","type":"journal-article","created":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T06:36:45Z","timestamp":1694932605000},"page":"2292","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The Regulatory Effects of JAK2\/STAT3 on Spermatogenesis and the Redox Keap1\/Nrf2 Axis in an Animal Model of Testicular Ischemia Reperfusion Injury"],"prefix":"10.3390","volume":"12","author":[{"given":"Abdullah","family":"Alnajem","sequence":"first","affiliation":[{"name":"Department of Medicine, Jaber Al-Ahmed Hospital, South Surra 47761, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8927-0485","authenticated-orcid":false,"given":"May","family":"Al-Maghrebi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Medicine, Kuwait University, Safat 13110, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"889959","DOI":"10.3389\/fendo.2022.889959","article-title":"Human Spermatogenesis: Insights from the Clinical Care of Men with Infertility","volume":"13","author":"Schlegel","year":"2022","journal-title":"Front. 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