Oxidative Stress-Related Programmed Cell Death in Male Infertility: Focussing on Ferroptosis

Area of Science:

• Reproductive biology
• Cellular stress responses
• Molecular toxicology

Background:

• Oxidative stress is a key factor in male infertility, impairing sperm production.
• Increased reactive oxygen species (ROS) trigger apoptosis and autophagy in testicular cells.
• Emerging evidence links ferroptosis to male germ cell death under oxidative stress.

Purpose of the Study:

• To review programmed cell death pathways (apoptosis, autophagy, ferroptosis) in testicular cells under oxidative stress.
• To highlight the role of ferroptosis in male infertility.
• To explore the interplay between these cell death mechanisms.

Main Methods:

• Literature review of studies on oxidative stress, male infertility, and programmed cell death.
• Analysis of mechanisms underlying apoptosis, autophagy, and ferroptosis in testicular cells.
• Focus on ferroptosis initiation and regulation.

Main Results:

• Oxidative stress induces apoptosis via caspases and autophagy in male germ cells.
• Ferroptosis, an iron-dependent, caspase-independent pathway, is triggered by GPX4 inactivation and system Xc- dysfunction.
• The balance of apoptosis, autophagy, and ferroptosis dictates testicular cell fate.

Conclusions:

• Apoptosis, autophagy, and ferroptosis are critical programmed cell death pathways in oxidative stress-induced testicular dysfunction.
• Ferroptosis represents a significant, under-explored mechanism contributing to male infertility.
• Targeting ferroptosis may offer novel therapeutic strategies for male reproductive disorders.