Testicular cancer (TC) represents the most common cancer affecting men within the
reproductive age and is often accompanied by major disturbances in semen parameters.
Cryopreservation is recommended in these patients before initiating cancer treatment.
Currently, there are no studies reporting the molecular mechanisms associated with
altered semen quality in these men. The main objective of this study was to compare
the sperm proteome of normozoospermic (motility >40%) and asthenozoospermic (motility
<40%) TC patients with normozoospermic infertile men without cancer (control group).
Pooled sperm samples from normozoospermic (n = 20), asthenozoospermic (n = 11) TC,
and a control group (n = 9) were used for quantitative global proteomic profiling
using liquid chromatography-tandem mass spectrometry. A total of 1085, 846, and 982
proteins were identified in normozoospermic TC, asthenozoospermic TC, and control
groups, respectively. Functional analysis revealed mitochondrial dysfunction and altered
cellular pathways in both normozoospermic and asthenozoospermic TC patients. Comparison
of pathway analysis showed no significant difference in fertility-associated proteins/mechanism
between the normozoospermic TC patients and infertile men. Western blot analysis revealed
under-expression of NDUFS1 associated with mitochondrial dysfunction and overexpression
of CD63 involved in sperm maturation in both normozoospermic and asthenozoospermic
TC patients. Our proteomic results confirm that defective cellular pathways are associated
with reproductive functions in both normozoospermic and asthenozoospermic TC patients
before the start of cancer treatment.