TF and TFRC regulate ferroptosis in swine testicular cells through the JNK signaling pathway.

Transferrin (TF) is a serum glycoprotein that plays a critical role in iron metabolism and typically functions through binding to its transferrin receptor (TFRC). TF is also considered a key indicator of sperm quality and, together with TFRC, plays a critical role in regulating spermatogenesis. This study aimed to explore the effects of increased TF and TFRC expression on ferroptosis in swine testicular cells (ST cells). Our findings revealed that the overexpression of either TF or TFRC diminishes ST cell viability, increases cytotoxicity, intensifies oxidative stress damage, decreases mitochondrial activity, and promotes ferroptosis. Transcriptomic analysis suggested that TF and TFRC may influence ST cells through the MAPK signaling pathway. Subsequent experiments revealed that inhibiting the JNK signaling pathway within the MAPK pathway improved mitochondrial activity, reduced oxidative stress damage, and mitigated ferroptosis progression. Moreover, we discovered that TF and TFRC might regulate cellular oxidative phosphorylation via the JNK signaling pathway. In conclusion, increased expression of TF or TFRC increases the sensitivity of ST cells to ferroptosis and modulates mitochondrial DNA transcription and energy metabolism through the JNK signaling pathway. These findings could offer potential therapeutic targets for addressing reproductive toxicity associated with ferroptosis.