Selenium-GPX4 Axis Relieves Arachidonic Acid-Induced Sperm Damage

Area of Science:

• Reproductive Biology
• Nutritional Biochemistry
• Toxicology

Background:

• Selenium (Se) and glutathione peroxidase 4 (GPX4) are critical for male reproductive health, involved in spermatogenesis and protection against oxidative damage.
• Arachidonic acid (AA) impacts male fertility, with excessive intake leading to adverse effects on sperm quality.
• The precise mechanisms by which the Se-GPX4 axis mitigates AA-induced testicular and sperm injury are not fully understood.

Purpose of the Study:

• To investigate how the Selenium-GPX4 axis ameliorates arachidonic acid-induced testicular and sperm injury.
• To elucidate the underlying molecular mechanisms, including omics-based approaches.

Main Methods:

• Establishment of an arachidonic acid-induced sperm injury model in vivo.
• Administration of Selenium (Se) supplementation.
• Utilisation of testicular-specific GPX4 knockout models.
• Comprehensive analysis using oxylipidomics and transcriptomics.

Main Results:

• Selenium supplementation significantly improved testicular and sperm quality in the AA-induced injury model by regulating GPX4 expression.
• GPX4 knockout exacerbated AA-induced testicular and sperm damage.
• Se-GPX4 axis intervention alleviated oxidative stress, apoptosis, sex hormone disorders, and inflammation.
• Oxylipidomics identified alterations in testicular polyunsaturated fatty acid (PUFA) metabolites, while transcriptomics highlighted key affected pathways.

Conclusions:

• The Se-GPX4 axis plays a crucial role in ameliorating AA-induced sperm damage.
• This protective effect involves regulating PUFA metabolism, activating glutathione metabolism, and mitigating oxidative stress, apoptosis, and inflammation.
• The axis also contributes to the repair of steroid hormone biosynthesis, thereby preserving male reproductive function.