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The homeostasis of the actin cytoskeleton in the spermatogenic epithelium is crucial for spermatogenesis. Actin cytoskeleton destruction in the seminiferous epithelium is one of the important reasons for BPA\u2010induced spermatogenesis disorder. However, the underlying molecular mechanisms remain largely unexplored. Herein, we explored the role and mechanism of Rsad2, an interferon\u2010stimulated gene in BPA\u2010induced actin cytoskeleton disorder in mouse GC\u20102 spermatocyte cell lines. After BPA exposure, the actin cytoskeleton was dramatically disrupted and the cell morphology was markedly altered accompanied by a significant increase in Rsad2 expression both in mRNA and protein levels in GC\u20102 cells. Furthermore, the phalloidin intensities and cell morphology were restored obviously when interfering with the expression of Rsad2 in BPA\u2010treated GC\u20102 cells. In addition, we observed a significant decrease in intracellular ATP levels after BPA treatment, while the ATP level was obviously upregulated when knocking down the expression of Rsad2 in BPA\u2010treated cells compared to cells treated with BPA alone. Moreover, Rsad2 relocated to mitochondria after BPA exposure in GC\u20102 cells. BPA promoted Rsad2 expression by activating type I IFN\u2010signaling in GC\u20102 cells. In summary, Rsad2 mediated BPA\u2010induced actin cytoskeletal disruption in GC\u20102 cells, which provided data to reveal the mechanism of BPA\u2010induced male reproductive toxicity.<\/jats:p>","DOI":"10.1002\/jat.4649","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T04:28:57Z","timestamp":1717388937000},"page":"1478-1488","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Rsad2 mediates Bisphenol A\u2010induced actin cytoskeletal disruption in mouse spermatocytes"],"prefix":"10.1002","volume":"44","author":[{"given":"Xiao","family":"Jiang","sequence":"first","affiliation":[{"name":"State Key Lab of Trauma and Chemical Poisoning, Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine Army Medical University  Chongqing 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