Are F2-isoprostanes a better marker of semen lipid peroxidation than MDA in reproductive pathologies with inflammatory basis?

Many male reproductive pathologies and a part of undiagnosed infertility share an oxidative stress (OS) etiology with high reactive oxygen species and cytokine concentrations. The lack of reliable biomarkers to quantify oxidative injury is a crucial problem in the field of male infertility. In this observational study, IL-1 beta and the OS markers malondialdehyde (MDA) and F-2-isoprostanes (F-2-IsoPs) were quantified in seminal plasma of 46 infertile patients with varicocele, genitourinary infections, idiopathic infertility, and 11 fertile men. Semen analysis was performed following WHO guidelines, IL-1 beta was determined by ELISA, MDA was quantified by HPLC, and F-2-IsoPs by GC/NICI-MS analysis. F-2-IsoPs were immunolocalized in spermatozoa of fertile and infertile subjects. Results indicated that F-2-IsoP, MDA, and IL-1 beta seminal levels positively correlated pairwise (p < 0.001) and showed negative correlations with sperm parameters (p < 0.001). Then, the studied population was grouped following the cause of infertility and the variables were compared between the different groups and a control sample. Seminal IL-1 beta, F-2-IsoPs, and MDA were significantly higher in varicocele (p < 0.001, for MDA p < 0.01) and genitourinary infections (p < 0.001, for IL-1 beta p < 0.01) groups than those observed in fertile subjects. F-2-IsoPs seemed to discriminate more accurately than MDA the different conditions, in particular idiopathic infertility. ROC curves demonstrated that the three analyzed indices were able to discriminate fertile and infertile patients. The immunofluorescence studies showed a low presence of F-2-IsoPs in spermatozoa of fertile men and an evident labeling in the tail, and cytoplasmic residues of spermatozoa from infertile patients. In conclusion, this data confirmed that F-2-IsoP level is a suitable marker of OS in seminal plasma, even more accurate than MDA and can be proposed for measuring OS in the clinical setting. © 2025 The Authors