The measurement of 8-hydroxy-2’-deoxyguanosine (8-OHdG) in seminal plasma is used as an additional lab test in the investigation of male infertility, recurrent pregnancy loss, and repeated failed IVF attempts, and preterm births. This test can be used in combination with DNA fragmentation, total antioxidant capacity (TAC), and reactive oxygen species (ROS), all measured in semen.
Oxidative stress is the major contributing cause of damage to sperm DNA. An early marker of DNA oxidation is the formation of base adducts such as 8-hydroxy-2’- deoxyguanosine (8-OHdG). DNA oxidation triggers activation of the base excision repair pathway (BER), which eliminates oxidized residues, such as 8-OHdG, via the 8-oxoguanine glycosylase 1 (OGG1) enzyme and inserts a new nucleotide on free 3’-OH ends using the APE1 protein. APE1 is not present in human spermatozoa, making it impossible to complete the BER pathway, which remains halted. However, the oocyte does possess DNA repair proteins APE1 and XRCC1, permitting the continuation of the BER pathway and effective DNA repair following fertilization. Since the oocyte is deficient in OGG1, non-resolution of sperm DNA 8-OHdG adducts means they will persist in the zygote and create the opportunity for mutations to occur prior to the initiation of embryonic development. Consistent with this situation, it has been reported that high sperm DNA oxidation can impair the oocyte’s ability to activate a normal developmental program. In this context, the assessment of sperm DNA oxidation should be of interest to manage male factor infertility associated with oxidative stress.
Several studies have shown that a high level of 8-OHdG, one of the best markers of DNA oxidation, in sperm is closely associated with semen quality parameters and male infertility. The 8-OHdG levels in seminal plasma are significantly correlated with semen volume, total sperm counts, and normal sperm morphology. The mean values of 8-OHdG level are also significantly higher in infertile subjects than in healthy fertile men.