title: Hydrogen peroxide modifies human sperm peroxiredoxins in a dose-dependent manner.
abstract: Low levels of reactive oxygen species (ROS) modulate signaling pathways required for human sperm activation, but high levels impair sperm function, leading to infertility. Peroxiredoxins (PRDXs) are enzymes with a dual role as ROS scavengers and modulators of ROS-dependent signaling. The present study aimed to characterize PRDXs in human spermatozoa and possible modifications resulting from hydrogen peroxide (H(2)O(2)). We found PRDX1, PRDX4, PRDX5, and PRDX6 in both seminal plasma and spermatozoa. Using immunocytochemistry, we demonstrated that these PRDXs are differentially localized in the head, acrosome, mitochondrial sheath, and flagellum. These observations were confirmed by immunoblotting using cytosolic, Triton-soluble and -insoluble, and head and flagella sperm fractions. PRDXs are dose-dependently modified by H(2)O(2), as seen by the formation of disulfide bridges and high-molecular-mass complexes. This first study, to our knowledge, on PRDXs in human spermatozoa indicates that PRDX1, PRDX4, PRDX5, and PRDX6 are modified when spermatozoa are challenged with H(2)O(2). This suggests that PRDXs may protect these cells at high levels of H(2)O(2) but could also control H(2)O(2) levels within different cell compartments so that normal sperm activation can occur.
authors.affiliation: Urology Research Laboratory, Urology Division, Faculty of Medicine, McGill University and Research Institute-McGill University Health Centre, Montréal, Québec, Canada. cristian.oflaherty@mcgill.ca
authors.forename: Cristian
authors.initials: C
authors.lastname: O'Flaherty
authors.forename: Angela Rico
authors.initials: AR
authors.lastname: de Souza
mesh_terms: D004305:Dose-Response Relationship, Drug; D006801:Humans; D006861:Hydrogen Peroxide / Q000008:administration & dosage*; D015151:Immunoblotting; D008297:Male; D016877:Oxidants / Q000008:administration & dosage*; D054465:Peroxiredoxin VI / Q000378:metabolism; D054464:Peroxiredoxins / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D013094:Spermatozoa / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D016877:Oxidants; D020033:Protein Isoforms; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; C515940:PRDX1 protein, human; C515980:PRDX4 protein, human; C515974:PRDX5 protein, human; C515977:PRDX6 protein, human; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins