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We studied the molecular mechanisms of 2,4\u2010D induced male reproductive system damage and the protective effects of <jats:italic>Lycium barbarum<\/jats:italic> polysaccharides (LBP) using Sprague Dawley rats and TM4 cells. Treatment with 2,4\u2010D caused architectural and functional changes in the testis, including collapsed and atrophied seminiferous tubules with reduced number of spermatozoa, scarce sperm in the epididymal duct, low levels of serum testosterone, decreased superoxide dismutase and glutathione peroxidase activity, high malondialdehyde content, and increased apoptosis in the testis and epididymis. The expression of Fas, FasL, FADD, Pro\u2010caspase\u20108, Cleaved\u2010Caspase\u20108, Pro\u2010Caspase\u20103, and Cleaved\u2010Caspase\u20103 were significantly increased in the testicular tissue of 2,4\u2010D\u2010treated rats. The proliferative activity of TM4 cells decreased with an increase in dose and time of 2,4\u2010D exposure, along with enhanced Fas\/Fas ligand expression and a decreased concentration of inhibin B in TM4 cell culture medium. Depletion of Fas by specific shRNA transfection reversed the effects of 2,4\u2010D in TM4 cells, further confirming the involvement of death receptor pathway in 2,4\u2010D\u2010mediated apoptosis of sertoli cells. Treatment with LBP also reversed the effects of 2,4\u2010D in testicular cells, resulting in improved cell architecture along with enhanced proliferative capacity. Moreover, in response to LBP treatment of Sertoli cells, the content of inhibin B increased, the level of reactive oxygen species and malondialdehyde decreased, the activities of superoxide dismutase and glutathione peroxidase increased, and the rate of apoptosis as well as the expression of Fas\/Fas ligand signaling pathway proteins decreased.<\/jats:p>","DOI":"10.1002\/tox.23635","type":"journal-article","created":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T09:24:00Z","timestamp":1659950640000},"page":"2764-2779","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Mechanism of 2,4\u2010Dichlorophenoxyacetic acid\u2010induced damage to rat testis via Fas\/FasL pathway and the protective effect of <scp><i>Lycium barbarum<\/i><\/scp> polysaccharides"],"prefix":"10.1002","volume":"37","author":[{"given":"Jian","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Occupational and Environmental 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