Nrf2 Levels in Human Semen and Spermatozoa: Association with F₂-Isoprostanes as Markers of Lipid Peroxidation

Despite the recognized role of oxidative stress (OS) in sperm function, limited data exist on Nuclear factor-E2-related factor 2 (Nrf2) pathway modulation in relation to reliable oxidative damage markers in human semen. In this study, 79 semen samples were collected from men undergoing semen analysis and grouped as varicocele (V, no. 22), urogenital infections (UI, no. 23), unknown fertility status without pathologies (UFS, no. 15), and fertile controls (F, no. 19). After semen analysis, ELISA were used to quantify F₂-Isoprostane (F₂-IsoPs) level, a marker of lipid peroxidation, and Nrf2 in seminal plasma and spermatozoa. The Nrf2 pathway (Keap1, Nrf2, Bach1, HO-1) was assessed in spermatozoa by qRT-PCR. Seminal plasma and sperm Nrf2 positively correlated with F₂-IsoPs (p < 0.001) and negatively with sperm vitality. Sperm Nrf2 also inversely correlated with progressive motility (p < 0.05). Seminal F₂-IsoP levels were lower in F than in the other groups. Sperm Nrf2 was significantly lower in F versus V and UI (p < 0.001) and UFS (p < 0.05), while seminal plasma Nrf2 levels did not differ among groups. qRT-PCR suggested Nrf2 pathway activation mainly in V and UI, consistent with increased OS. Elevated F₂-IsoPs, a marker of poor sperm quality, and sperm Nrf2 could suggest OS-driven Nrf2 activation, providing complementary biomarkers of oxidative status in male reproductive health.