Cadmium induced inflammation and apoptosis of porcine epididymis via activating RAF1/MEK/ERK and NF-κB pathways

Cadmium (Cd) was a serious heavy metal pollutant. Cd exposure will cause damage to reproductive organs. It was largely unknown whether Cd exposure caused inflammation and apoptosis in epididymis. In this study, we established models of Cd exposure in swine, and the apoptotic level of epididymis was detected by in situ TUNEL fluorescence staining assay, the results showed that Cd exposure significantly increased TUNEL-apoptosis index. Furthermore, the results of qRT-PCR and Western blot showed that Cd activated the proto-oncogenic serine/threonine kinase-1 (RAF1)/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signal pathway (RAF1/MEK/ERK) and led to the subsequent up-regulation of the nuclear factor-kappa B (NF-kappa B), tumor necrosis factor alpha (TNF-alpha), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), caused inflammation in epididymis. NF-kappa B inflammation pathway also mediated the tumor protein P53 (P53) and indirectly activated the Cytochrome c (Cytc), B-cell lymphoma-2 (Bcl-2), Bcl-2-Associated X protein (Bax), Caspase 3, Caspase 9. In summary, we believed that the RAF1/MEK/ERK pathway came into play in the apoptosis of epididymal tissues exposed to Cd by activating the NF-kappa B Inflammation pathway, followed by activation of the mitochondrial apoptotic pathway. This study provides more abundant data for exploring the reproductive toxicity of Cd.

Automated summary

This study revealed that cadmium exposure caused inflammation and apoptosis in epididymal tissues. The activation of the RAF1/MEK/ERK pathway and subsequent up-regulation of NF-kappa B played a crucial role in these processes. This research provides valuable insights into the reproductive toxicity of cadmium.