Proteomic Signatures Reveal Differences in Stress Response, Antioxidant Defense and Proteasomal Activity in Fertile...

Area of Science:

• Reproductive Biology
• Oxidative Stress Research
• Proteomics

Background:

• Elevated reactive oxygen species (ROS) are a primary cause of male infertility.
• Some men with high seminal ROS levels remain fertile, suggesting protective mechanisms exist.

Purpose of the Study:

• To elucidate the molecular mechanisms preserving fertility in men with high seminal ROS.
• To identify differentially expressed proteins (DEPs) in seminal plasma and spermatozoa associated with fertility despite high ROS.

Main Methods:

• Proteomic analysis of seminal plasma and spermatozoa from fertile men with low (control) and high (ROS+) ROS levels.
• Comparison of DEPs between control and ROS+ groups.
• Validation of specific protein expression changes using Western blot (WB).

Main Results:

• Identified 44 DEPs in seminal plasma and 371 DEPs in spermatozoa between groups.
• DEPs were mainly involved in oxidoreductase, endopeptidase inhibitor, and antioxidant activities.
• Validated underexpression of NADH:ubiquinone oxidoreductase core subunit S1 and overexpression of superoxide dismutase 1 and peroxiredoxin 4 in ROS+ spermatozoa.

Conclusions:

• Fertile men with high ROS exhibit a robust antioxidant defense system protecting sperm proteins.
• An active proteasomal system aids in degrading defective proteins, contributing to maintained fertility.
• These findings highlight the complex molecular adaptations enabling fertility under oxidative stress.