Increased sperm DNA damage in patients with varicocele: relationship with seminal oxidative stress

TLDR

The pathophysiology of testicular damage in varicocele remains incompletely understood, and oxidative stress leading to sperm DNA damage is a major contributor to male infertility. The study aimed to quantify sperm nuclear DNA damage in varicocele patients and assess its association with oxidative stress. Semen from 55 varicocele patients and 25 controls were classified per WHO criteria, and sperm DNA damage was measured by SCSA/flow cytometry and TUNEL, while ROS and antioxidant capacity were quantified by chemiluminescence. Varicocele patients exhibited significantly higher sperm DNA fragmentation and TUNEL positivity, along with elevated ROS levels, indicating that oxidative damage correlates with increased sperm DNA damage even when semen parameters appear normal.

Abstract

The pathophysiology of the testicular damage in varicocele has not been completely understood. Oxidative stress and related sperm DNA damage have been identified as significant causes of male infertility. The current study was designed to determine the extent of sperm nuclear DNA damage in patients with varicocele and to examine its relationship with oxidative stress.Semen samples from 55 patients with clinical varicocele and 25 normozoospermic donors were examined. Varicocele sperm samples were classified as normal or abnormal according to World Health Organization guidelines. Sperm DNA damage was evaluated by the sperm chromatin structure assay/flow cytometry and by the terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) assay. Levels of reactive oxygen species (ROS) and total antioxidant capacity were assessed by a chemiluminescence assay.DNA fragmentation index (DFI) (percentage of sperm with denatured DNA) values and the percentage of TUNEL-positive cells were significantly greater in patients with varicocele, either with normal (DFI, 20.7 +/- 4.0; TUNEL positive, 26.1 +/- 3.2) or with abnormal (DFI, 35.5 +/- 9.0; TUNEL positive, 32.2 +/- 4.1) semen profile, compared with controls (DFI, 7.1 +/- 0.9; TUNEL positive, 14.2 +/- 1.2). Similarly, ROS levels were significantly higher (P < 0.01) in both groups of patients with varicocele.The presence of a varicocele is associated with high levels of DNA-damage spermatozoa even in the presence of normal semen profile. The results also indicate that oxidative damage is associated with sperm DNA damage in these patients.