Oxidative DNA Damage in Male Germ Cells in Normozoospermic Infertile Men: A Case for Concern

Background: Sperm DNA is highly susceptible to oxidative damage due to various endogenous/exogenous factors and deficient DNA damage detection and repair mechanisms. Telomeres are the favourable targets for oxidative damage. So, this study was planned to evaluate seminal oxidative stress, sperm DNA damage and sperm telomere length in normozoospermic infertile men. Material and Method: The study included 30 infertile men and 30 controls. Reactive oxygen species (ROS) estimation was done by chemiluminesence method and 8-isoprostane (8-IP) and 8-hydroxy-2-deoxy-guanosine (8-OHdG) levels by ELISA. The average sperm telomere length was measured using quantitative Real Time PCR method. Sperm Chromatin Structure Assay (SCSA) was done by flow cytometry. Results: Mean ROS (89.43±36.32 Vs. 15.04 ± 10.81 RLU/sec/million sperm; p=0.016) and 8-IP levels (698.7 ± 127.8 Vs. 278.02 ± 72.03 pg/ml; p=0.035) were significantly elevated in cases as compared to controls. 8−OHdG levels were higher in patients (25.33 ± 13.34 pg/ml) as compared to controls (15.34 ± 8.3 pg/ml) (p= 0.032). Mean DNA Fragmentation Index (DFI %) in patients was 40.31 ± 14.83, which was higher as compared to controls (24.43 ± 8.83) (p<0.0001). Mean telomere length was significantly (p=0.012) lower in patient group (0.737 ± 0.038) as compared to fertile control group (0.787 ± 0.054). Conclusion: Normozoospermic infertile men may experience seminal oxidative stress, DNA damage and telomere shortening. Oxidative stress, loss of sperm DNA integrity, accumulation of mutagenic bases, telomere shortening may lead to genome hyper mutability and may be the underlying aetiology of male infertility. As majority of causes leading to oxidative stress are modifiable/ treatable (sedentary life style, excessive alcohol intake, smoking, excessive use of cell phone, acute or chronic infections, varicocele), management of oxidative stress may minimize free radical levels and subsequent oxidative damage to sperm DNA. Thus sperm with its limited antioxidant/DNA repair capacity may benefit by adopting a policy of prevention is better than cure.