Cadmium (Cd) can cause reproductive disorders through epididymal injury. However, the specific molecular mechanism of Cd-induced epididymal toxic injury is rarely reported. In this study, the model of Cd poisoning in pig epididymis was established. Ten 6-week-old male piglets were divided into two groups. The control group was fed a basic diet, while the Cd group received a diet supplemented with 20 mg/kg CdCl2. After 40 days, All piglets were euthanized, and epididymal tissues were collected to detect morphological changes, trace element contents, oxidative stress (OS) parameters, toll like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling pathway and necroptosis marker genes. This study showed that Cd led to an increased concentration of Cd element in pig epididymis. According to morphological observation, pig epididymal tissue in the Cd group was damaged. Cd decreased the contents of glutathione (GSH), total antioxidant capacity (T-AOC), catalase (CAT), dismutase (SOD), and glutathione peroxidase (GSH-px), but the contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA) were increased. Additionally, Caspase 8 expression was decreased, whereas the expression of TLR4, NF-κB, FADD, RIPK1, RIPK3, MLKL and heat shock proteins (HSPs) were increased after Cd stimulation. We concluded that Cd-triggered TLR4/NF-κB signaling pathway and oxidative stress potentially promoted necroptosis in pig epididymis.

中文翻译：

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镉暴露通过猪附睾中的 TLR4/NF-κB 信号通路诱导氧化应激介导的坏死性凋亡


镉 （Cd） 可通过附睾损伤引起生殖障碍。然而，Cd 诱导的附睾毒性损伤的具体分子机制很少报道。本研究建立了猪附睾 Cd 中毒模型。将 10 头 6 周龄雄性仔猪分为 2 组。对照组饲喂基本饮食，而 Cd 组饲喂补充 20 mg/kg CdCl2 的饮食。40 d后，对所有仔猪实施安乐死，收集附睾组织，检测形态变化、微量元素含量、氧化应激（OS）参数、收费样受体4（TLR4）/核因子κB（NF-κB）信号通路和坏死性凋亡标志基因。这项研究表明，Cd 导致猪附睾中 Cd 元件的浓度增加。根据形态学观察，Cd 组猪附睾组织受损。Cd 降低了谷胱甘肽 （GSH） 、总抗氧化能力 （T-AOC） 、过氧化氢酶 （CAT） 、歧化酶 （SOD） 和谷胱甘肽过氧化物酶 （GSH-px） 的含量，但过氧化氢 （H2O2） 和丙二醛 （MDA） 的含量增加。此外，Cd 刺激后 Caspase 8 表达降低，而 TLR4 、 NF-κB 、 FADD 、 RIPK1 、 RIPK3 、 MLKL 和热休克蛋白 （HSP） 的表达增加。我们得出结论，Cd 触发的 TLR4/NF-κB 信号通路和氧化应激可能促进猪附睾坏死性凋亡。