Epididymal Secretory Glutathione Peroxidase (GPX5): A Dual Role in Sperm Oxidative Stress Response

The epididymal secretory glutathione peroxidase (GPX5), encoded by the GPX5 gene, is known to play a dual role in the oxidative stress response of sperm. Aitken et al. have demonstrated that this enzyme acts as an antioxidant in seminal plasma, protecting sperm cells from oxidative damage. Additionally, research has shown that GPX5 is upregulated in low-quality boar sperm, thought to be a compensatory mechanism for the increased susceptibility to oxidative damage in such sperm. Another possibility is that the high levels of reactive oxygen species (ROS) in the semen activate the body's defense system against oxidative stress, leading to an increase in the expression of the Glutathione peroxidase 4 isoform A precursor (GPX4) in ROS+ sperm samples to mitigate the effects of oxidative stress. Surprisingly, even after multiple rounds of centrifugation and washing, higher levels of expression of GPX5, as well as the upregulation of Glutaredoxin (P12309) encoded by GLRX and Dehydrogenase/reductase SDR family member 4 (Q8WNV7) encoded by DHRS4, were still detected in the PRE group. Morgan et al. conducted a proteomic study of selenium-treated C. elegans and found that GSH activation of GLRX-21 might be required to reduce selenium-induced oxidative stress and lower the mortality rate. Moreover, selenite detoxification is facilitated by selenophosphate synthetase 2 (SEPHS2) (A1YIZ1). As ROS can trigger lipid peroxidation in membranes, releasing highly reactive carbonyl compounds, DHRS4 first detoxifies these compounds to perform its oxidative stress defense function. Secondly, the higher levels of testosterone and steroid hormones may be related to a lower percentage of active sperm during sexual activity. We can speculate that, as a key gene involved in cell ketone and steroid metabolism, high levels of DHRS4 expression may accelerate sperm cell apoptosis. In addition, the flagellar glycolytic enzyme ENO4 (F1S4S3) regulates energy metabolism, which may be necessary for sperm vitality and function. These results suggest that the PRE group of sperm may be exposed to oxidative stress early on and produce defense mechanisms through proteins such as O18994, P12309, and Q8WNV7. However, this also accelerates ketone, reproductive hormone, and energy metabolism, which in turn accelerates cell death, leading to decreased sperm viability under 17°C conditions.