Spermatozoa Proteins Involved in ROS Generation and Antioxidant Defense Are Differentially Acetylated in Idiopathic...

Area of Science:

• Reproductive Biology
• Proteomics
• Molecular Biology

Background:

• Idiopathic male infertility (IMI) affects 50% of cases, with current semen analysis unable to detect molecular causes.
• Post-translational modifications, like lysine acetylation, are vital for sperm function, influencing energy metabolism and antioxidant defenses.

Purpose of the Study:

• To investigate global lysine acetylation patterns in spermatozoa from idiopathic infertile patients (IIP) compared to fertile donors (FD).
• To identify key proteins and pathways affected by dysregulated acetylation in IMI.

Main Methods:

• Global acetyl-proteomic profiling of spermatozoa using immunoprecipitation and LC-MS/MS.
• Bioinformatics analysis (STRING, Cytoscape, IPA) to identify differentially acetylated proteins (DAPs) and enriched pathways.
• Western blot validation of identified hub proteins.

Main Results:

• Identified 718 differentially acetylated proteins (DAPs) in IIP.
• Significant enrichment of pathways related to redox homeostasis, molecular transport, glycolysis, and mitochondrial metabolism.
• Hub proteins (SOD1, PARK7, PRKACA) were downregulated in IIP, linking oxidative stress to impaired sperm motility and function.

Conclusions:

• Dysregulated lysine acetylation is a molecular hallmark of idiopathic male infertility.
• Aberrant acetylation affects critical sperm functions, including redox balance and mitochondrial metabolism.
• Targeting acetylation pathways could lead to novel diagnostic biomarkers and therapeutic strategies for male infertility.