Glutathione peroxidase 3 (extracellular isoform) levels and functional polymorphisms in fertile and infertile men

Oxidative stress has an undeniable role in the impairment of sperm function and idiopathic male infertility. On the other hand, the local antioxidant system particularly glutathione peroxidase 3 (GPX3) as an extracellular enzyme protects male fertility from oxidative damages. Therefore, in the current study, we evaluated the association between two functional polymorphisms of the GPX3 gene with its levels in seminal fluid and subsequently with the risk of male infertility. We recruited 100 fertile and 100 infertile men for the study. Our results showed that the concentration of GPX3 was higher in the fertile group than infertile patients (p= <0.01), and there were positive correlations between GPX3 concentration in seminal fluid with sperm motility and morphology. The frequency of rs8177404 and rs3828599 genotypes and alleles was significantly different between the groups and we found that having the rs8177404 polymorphism (TC and CC genotypes) could increase the risk of idiopathic infertility more than 2-fold. On the other hand, the GG genotype (rs3828599) showed a protective effect against infertility. Our results demonstrated that men carrying CC genotype of rs8177404 polymorphism had significantly lower progressively motile sperm and higher immotile sperm compared with subjects carrying TT and TC genotypes. In the rs3828599 polymorphism, the GG carriers had significantly higher progressively motile and lower immotile sperm than AA carriers. Furthermore, men with genotypes of CC (rs8177404) and GG (rs3828599) had significantly lower and higher levels of GPX3 in the seminal fluid, respectively. In conclusion, our results showed associations between sperm parameters with GPX3 levels and the gene polymorphisms. It seems rs8177404 and rs3828599 polymorphisms can affect GPX3 levels in seminal fluid and subsequently sperm parameters.