Ferroptosis is a newly identified form of cell death characterized by accumulation of intracellular iron and requirement of lipid peroxidation. However, whether arsenite triggers testicular cell death via ferroptosis remains unclear. In this study, after administrating of adult male mice with 0.5, 5 and 50 mg/L arsenite for six months via drinking water, the results showed that arsenite caused the pathological changes in mouse testis and significantly reduced the number of sperm. Mitochondrial injuries were observed as the major ultrastructural damages induced by arsenite, and these damages were accompanied by the apparent mitochondrial oxidative damage in the testis, manifested by accumulation of iron, production of reactive oxygen species and lipid peroxidation products. We also demonstrated that arsenite significantly activated ferroptosis-related signal pathways in the mouse testis. To further verify the results obtained in the animal model, GC-2spd cells were employed as the in vitro culture system. Consistently, the results revealed arsenite remarkably triggered the ferroptotic cell death in vitro, and inhibition of ferroptosis by ferrostatin-1 could attenuate this adverse effect in cells. These findings together indicate that arsenite can trigger oxidative stress thus leading to testicular cell death by ferroptosis, suggesting that inhibition of ferroptosis would be a potential strategy for treatment of arsenite-related male reproductive toxicity.

Ferroptosis是一种新发现的细胞死亡形式，其特征是细胞内铁的积累和脂质过氧化的需求。然而，亚砷酸盐是否通过肥大症触发睾丸细胞死亡尚不清楚。在这项研究中，成年雄性小鼠通过饮用水施用0.5、5和50 mg / L的亚砷酸盐六个月后，结果表明，亚砷酸盐会引起小鼠睾丸的病理变化，并显着减少精子数量。观察到线粒体损伤是由亚砷酸盐引起的主要超微结构损伤，这些损伤伴随着睾丸中明显的线粒体氧化损伤，表现为铁的积累，活性氧的产生和脂质过氧化产物。我们还证明了亚砷酸盐在小鼠睾丸中显着激活了与肥大症相关的信号通路。为了进一步验证在动物模型GC-2中获得的结果spd细胞用作体外培养系统。一致地，结果表明亚砷酸盐在体外显着触发了肥大细胞的死亡，而ferrostatin-1对肥大细胞的抑制作用可以减轻这种不良作用。这些发现共同表明，亚砷酸盐可以触发氧化应激，从而导致通过肥大化而导致睾丸细胞死亡，这表明抑制肥大化将成为治疗与砷相关的男性生殖毒性的潜在策略。