Altered Molecular Pathways in the Proteome of Cryopreserved Sperm in Testicular Cancer Patients before Treatment

Area of Science:

• Reproductive Biology
• Oncology
• Proteomics

Background:

• Testicular cancer (TC) is the most common cancer in men of reproductive age.
• TC often leads to significant semen parameter disturbances, necessitating sperm cryopreservation before treatment.
• Molecular mechanisms underlying altered semen quality in TC patients remain largely unexplored.

Purpose of the Study:

• To compare the sperm proteome of normozoospermic and asthenozoospermic TC patients with normozoospermic infertile men (control group).
• To identify molecular mechanisms associated with altered semen quality in TC patients.

Main Methods:

• Quantitative global proteomic profiling using liquid chromatography-tandem mass spectrometry on pooled sperm samples.
• Analysis included normozoospermic TC (n=20), asthenozoospermic TC (n=11), and control (n=9) groups.
• Functional and pathway analyses, along with Western blot validation.

Main Results:

• Identified 1085, 846, and 982 proteins in normozoospermic TC, asthenozoospermic TC, and control groups, respectively.
• Revealed mitochondrial dysfunction and altered cellular pathways in both TC patient groups.
• Showed no significant difference in fertility-associated proteins between normozoospermic TC patients and controls.
• Western blot confirmed NDUFS1 under-expression (mitochondrial dysfunction) and CD63 over-expression (sperm maturation) in TC patients.

Conclusions:

• Defective cellular pathways, including mitochondrial dysfunction, are linked to reproductive function in TC patients prior to cancer treatment.
• Proteomic analysis provides insights into molecular alterations affecting sperm quality in testicular cancer.
• Findings highlight potential targets for understanding and managing fertility issues in TC survivors.