Comparison of Oxidative Stress/DNA Damage in Semen and Blood of Fertile and Infertile Men

Abstract

Abnormal spermatozoa frequently display typical features of oxidative stress, i.e. excessive level of reactive oxygen species (ROS) and depleted antioxidant capacity. Moreover, it has been found that a high level of oxidatively damaged DNA is associated with abnormal spermatozoa and male infertility. Therefore, the aim of our study was the comparison of oxidative stress/DNA damage in semen and blood of fertile and infertile men. The broad range of parameters which describe oxidative stress and oxidatively damaged DNA and repair were analyzed in the blood plasma and seminal plasma of groups of fertile and infertile subjects. These parameters include: (i) 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanine (8-oxoGua) levels in urine; (ii) 8-oxodG level in DNA isolated from leukocytes and spermatozoa; (iii) antioxidant vitamins (A, C and E) and uric acid. Urinary excretion of 8-oxodG and 8-oxoGua and the level of oxidatively damaged DNA in leukocytes as well as the level of antioxidant vitamins were analyzed using HPLC and HPLC/GC/MS methods.The results of our study demonstrate that 8-oxodG level significantly correlated with every parameter which describe sperm quality: sperm count, motility and morphology. Moreover, the data indicate a higher level of 8-oxodG in sperm DNA compared with DNA of surrogate tissue (leukocytes) in infertile men as well as in healthy control group. For the whole study population the median values of 8-oxodG/106 dG were respectively 7.85 and 5.87 (p = 0.000000002). Since 8-oxodG level in sperm DNA is inversely correlated with urinary excretion rate of 8-oxoGua, which is the product of OGG1 activity, we hypothesize that integrity of spermatozoa DNA may be highly dependent on OGG1 activity. No relationship between the whole body oxidative stress and that of sperm plasma was found, which suggests that the redox status of semen may be rather independent on this characteristic for other tissues.

Semen leukocytes and oxidative-dependent DNA damage of spermatozoa in male partners of subfertile couples with no symptoms of genital tract infection

“…Intriguingly, although the expression of 8-OHdG was significantly associated to sperm DNA fragmentation and to a lower sperm concentration (Table 4), both parameters explained 19% only of the variation in the percentage of 8-OHdG-positive spermatozoa at the multivariate analysis. Therefore, the presence of an oxidative-related DNA damage of ejaculated spermatozoa in a population of men attending a fertility clinic and asymptomatic for a genital tract infection was faintly associated to an altered semen quality as already suggested (Kodama et al, 1997;Ni et al, 1997;Shen et al, 1999;Kao et al, 2008;Zribi et al, 2011;Cambi et al, 2013;Guz et al, 2013) and it should be present in alive and motile spermatozoa with no DNA fragmentation. An oxidative stress may result in the presence of 8-OHdG adducts in the DNA of ejaculated potentially fertile spermatozoa.…”

Investigation on the Origin of Sperm DNA Fragmentation: Role of Apoptosis, Immaturity and Oxidative Stress

“…Similarly, ROS could break the DNA backbone directly, but also act as triggers of apoptotic pathways ending in caspases and apoptotic nucleases activation, as happens in somatic cells (16). The above hypotheses are supported by indirect studies showing that infertile/ subfertile subjects who are known to have increased levels of sDF show higher degrees of cell immaturity (17) or of apoptotic features (18)(19)(20) or of oxidative stress (21,22) in their ejaculates and by correlative studies reporting associations between the levels of sDF and signs of impaired chromatin maturation, (23,24) or apoptotic traits (25,26) or evidence of oxidative stress (27,28). However, these approaches detect the markers of the hypothesized mechanisms in different semen aliquots from those used to reveal sDF and the occurrence of statistical correlations does not necessarily imply a cause-effect relationship.…”

Asociación entre obesidad abdominal y daño oxidativo seminal en pacientes con síndrome metabólico

“…De hecho, el estrés oxidativo es ampliamente reconocido como una de las principales causas de infertilidad masculina 8 . De manera más detallada, niveles elevados de marcadores de daño oxidativo del ADN se asocia a malformaciones espermáti-cas 22 . Asimismo, la acción de las ROS sobre fosfolípidos poliinsaturados de membrana espermática se ha asociado a malformaciones y afectación de la movilidad 23 .…”