Year: 2025
Type: article
Abstract: Background: While Pyrotinib is effective in treating human epidermal growth factor receptor 2 (HER2)-positive breast cancer, its impact on male reproductive health remains unclear. This study investigates the potential reproductive toxicity and underlying mechanisms of Pyrotinib in male Leydig cells, key regulators of testosterone production. Methods: Leydig cells were treated with Pyrotinib, with 0.1‰ dimethyl sulfoxide (DMSO)-treated cells serving as the control group, to evaluate its effects on cell viability, apoptosis, cell cycle progression and signaling pathways. Clonogenic assays, flow cytometry, Western blotting and transcriptome sequencing were employed. Results: Pyrotinib treatment for 24 hours significantly reduced cell viability and colony formation while increasing apoptosis. Flow cytometry revealed G1 phase arrest in 67.2% of cells after Pyrotinib exposure. Western blot analysis showed transient activation of Ak strain transforming (AKT) and extracellular signal-regulated kinase (ERK) at 2 hours, followed by marked inhibition at 24–48 hours. Transcriptomic analysis identified 197 downregulated genes enriched in chromatin organization and mitotic processes, particularly cell cycle regulation. Conclusions: Pyrotinib impairs Leydig cell proliferation through G1 arrest and inhibition of the phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK)/ERK pathways, along with downregulation of cell cycle-related genes. These findings highlight the need for further evaluation of Pyrotinib’s reproductive safety in male patients.
Source: Journal of Men s Health
Authors: Xiao Hu, Zhongjian Pan, Jie Yang, Peng Zheng, Jian Tan, Zhipeng Xu, Huaming Tang, Jianpeng Hu
Institution: Jiangsu University
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,500
OpenAlex ID: W4412763475