Microcystin-leucine-arginine (MC-LR) has been identified to be a hazardous material to cause hepatotoxicity. In this study, mice were exposed to MC-LR dissolved in drinking water at doses of 1, 10, 20 and 30 μg/L for 90 and 180 days, respectively. We validated MC-LR accelerated spermatid exfoliation and caused large vacuoles in testes, reducing sperm count and increasing percentage of morphologically abnormal sperm. Furthermore, we found MC-LR induced the apical ectoplasmic specialization (ES) disassembly by disrupting F-actin organization. Further studies identified that downregulation of Palladin, the actin crosslinking protein, might be associated with disassembly of the apical ES in mice testis following MC-LR exposure. We also confirmed that MC-LR disrupted the interaction between Palladin and other actin-related proteins and thus impeded the F-actin organization. Additionally, we found that autophagy initiated by AMPK/ULK1 signaling pathway mediated the degradation of Palladin in Sertoli cells challenged with MC-LR. Following exposure to MC-LR, reduced PP2A activity and upregulated expression of LKB1 and CAMKK2 could activate AMPK. In conclusion, these results revealed MC-LR induced the degradation of Palladin via AMPK/ULK1-mediated autophagy, which might result in the apical ES disorder and spermatid exfoliation from spermatogenic epithelium. Our work may provide a new perspective to understand MC-LR-induced male infertility.

微囊藻蛋白-亮氨酸-精氨酸（MC-LR）已被确定为引起肝毒性的危险物质。在这项研究中，小鼠分别暴露于溶于饮用水的MC-LR中，剂量分别为1、10、20和30μg/ L，分别为90天和180天。我们验证了MC-LR加速了精子剥脱并在睾丸中引起了大的液泡，从而减少了精子数量并增加了形态异常精子的百分比。此外，我们发现MC-LR通过破坏F-肌动蛋白组织诱导了根尖胞浆特化（ES）拆卸。进一步的研究表明，MC-LR暴露后，肌动蛋白交联蛋白Palladin的下调可能与小鼠睾丸中根尖ES的分解有关。我们还证实，MC-LR破坏了Palladin与其他肌动蛋白相关蛋白之间的相互作用，从而阻碍了F-肌动蛋白的组织。此外，我们发现由AMPK / ULK1信号通路启动的自噬介导了MC-LR攻击的Sertoli细胞中Palladin的降解。暴露于MC-LR后，降低的PP2A活性以及LKB1和CAMKK2的表达上调可以激活AMPK。总之，这些结果表明，MC-LR通过AMPK / ULK1介导的自噬诱导帕拉丁素的降解，这可能导致根尖ES紊乱和生精上皮剥落。我们的工作可能为了解MC-LR引起的男性不育症提供新的视角。我们发现，由AMPK / ULK1信号通路启动的自噬介导了MC-LR攻击的Sertoli细胞中Palladin的降解。暴露于MC-LR后，降低的PP2A活性以及LKB1和CAMKK2的表达上调可以激活AMPK。总之，这些结果表明，MC-LR通过AMPK / ULK1介导的自噬诱导帕拉丁素的降解，这可能导致根尖ES紊乱和生精上皮剥落。我们的工作可能为了解MC-LR引起的男性不育症提供新的视角。我们发现，由AMPK / ULK1信号通路启动的自噬介导了MC-LR攻击的Sertoli细胞中Palladin的降解。暴露于MC-LR后，降低的PP2A活性以及LKB1和CAMKK2的表达上调可以激活AMPK。总之，这些结果表明，MC-LR通过AMPK / ULK1介导的自噬诱导帕拉丁素的降解，这可能导致根尖ES紊乱和生精上皮剥落。我们的工作可能为了解MC-LR引起的男性不育症提供新的视角。这可能会导致根尖ES疾病和生精上皮剥落。我们的工作可能为了解MC-LR引起的男性不育症提供新的视角。这可能会导致根尖ES疾病和生精上皮剥落。我们的工作可能为了解MC-LR引起的男性不育症提供新的视角。