The toxicity and mechanisms of pyrotinib on male reproductive system

While Pyrotinib has proven effective in treating HER2-positive breast cancer, its impact on male patients is not well-studied. This research examines the potential toxicity of Pyrotinib on the male reproductive system using mouse Leydig cells. Our results indicate that 24 hours of Pyrotinib treatment significantly increased apoptosis and decreased cell viability. Clonogenic assays showed a marked reduction in colony formation, and flow cytometry analysis revealed that 67.2% of the treated cells were in the G1 phase, suggesting hindered progression into the S phase. Western blot analysis demonstrated an initial rise in phosphorylated AKT and ERK, which was followed by a notable decline in these phosphorylated proteins after extended treatment, indicating the involvement of specific pathways in the drug's effects. Transcriptome sequencing identified a downregulation of 197 genes due to Pyrotinib treatment, with these genes enriched in processes related to chromatin and mitosis, particularly in pathways linked to the cell cycle. These findings imply that Pyrotinib inhibits cell proliferation through various molecular mechanisms, underscoring the necessity for further research into its safety and effects on male reproductive health.