Changes in Sperm Glutathione and Glutathione Redox States Correlate to Poor Sperm Qualitative Measures

Background/Objectives: In the past 50 years, human reproductive capacity has steadily declined with elusive and idiopathic origins. Amongst theorized causes, oxidative stress has been proposed to directly contribute to male infertility. The glutathione (GSH) and glutathione disulfide (GSSG) molecular couple reflect cellular redox environments and are thus reflective of oxidative stress in most cells. Shifting GSH/GSSG redox states to abnormal, more oxidizing conditions can disrupt normal cellular activities. This study explores the correlation between the GSH/GSSG redox system and factors involved in male infertility, including sperm quality, specifically sperm motility and total count. Methods: Semen samples from 98 patients underwent high-performance liquid chromatography (HPLC) for GSH/GSSG analysis. A protein assay determined the protein concentration for normalization, and GSH/GSSG redox potentials (Eh) were calculated using the Nernst equation. Results: A significant inverse correlation between GSH/GSSG Eh and sperm count was identified (p = 0.0046 and R2 = 0.071). Analysis also found that cellular GSH concentrations (p < 0.001 and R2 = 0.11) and total GSH (GSH + (GSSG × 2); p = 0.0039 and R2 = 0.074) were significantly and positively correlated with total sperm count, whereas GSSG concentrations were not. The correlation between redox potential and motility was not significantly different (p = 0.11 and R2 = 0.02). Conclusions: This study shows that total sperm count decreases with increasing redox potential, indicating that more oxidized systems, such as the GSH/GSSG system, are associated with lower sperm counts in ejaculated sperm samples. These findings support a potential link between oxidative stress and sperm parameters. As understanding of the relationship between GSH/GSSG Eh and sperm quality improves, this may inform future potential therapies and approaches aimed at supporting male reproductive health.