Peroxiredoxin 6 is the primary antioxidant enzyme for the maintenance of viability and DNA integrity in human spermatozoa

FERNANDEZ, MARIA C; O?FLAHERTY, CRISTIAN

HUMAN REPRODUCTION

OXFORD UNIV PRESS

Año: 2018 vol. 33 p. 1394 - 1407

0268-1161

AbstractSTUDY QUESTION:Are all components of the peroxiredoxins (PRDXs) system important to control the levels of reactive oxygen species (ROS) to maintain viability and DNA integrity in spermatozoa?SUMMARY ANSWER:PRDX6 is the primary player of the PRDXs system for maintaining viability and DNA integrity in human spermatozoa.WHAT IS KNOWN ALREADY:Mammalian spermatozoa are sensitive to high levels of ROS and PRDXs are antioxidant enzymes proven to control the levels of ROS generated during sperm capacitation to avoid oxidative damage in the spermatozoon. Low amounts of PRDXs are associated with male infertility. The absence of PRDX6 promotes sperm oxidative damage and infertility in mice.STUDY DESIGN, SIZE, DURATION:Semen samples were obtained over a period of one year from a cohort of 20 healthy non-smoking volunteers aged 22-30 years old.PARTICIPANTS/MATERIALS, SETTING, METHODS:Sperm from healthy donors was incubated for 2 h in the absence or presence of inhibitors for the 2-Cys PRDXs system (peroxidase, reactivation system and NADPH-enzymes suppliers) or the 1-Cys PRDX system (peroxidase and calcium independent-phospholipase A2 (Ca2+-iPLA2) activity). Sperm viability, DNA oxidation, ROS levels, mitochondrial membrane potential and 4-hydroxynonenal production were determined by flow cytometry.MAIN RESULTS AND THE ROLE OF CHANCE:We observed a significant decrease in viable cells due to inhibitors of the 2-Cys PRDXs, PRDX6 Ca2+-iPLA2 activity or the PRDX reactivation system compared to controls (P ≤ 0.05). PRDX6 Ca2+-iPLA2 activity inhibition had the strongest detrimental effect on sperm viability and DNA oxidation compared to controls (P ≤ 0.05). The 2-Cys PRDXs did not compensate for the inhibition of PRDX6 peroxidase and Ca2+-iPLA2 activities.LARGE SCALE DATA:Not applicable.LIMITATIONS, REASONS FOR CAUTION:Players of the reactivation systems may differ among mammalian species.WIDER IMPLICATIONS OF THE FINDINGS:The Ca2+-iPLA2 activity of PRDX6 is the most important and first line of defense against oxidative stress in human spermatozoa. Peroxynitrite is scavenged mainly by the PRDX6 peroxidase activity. These findings can help to design new diagnostic tools and therapies for male infertility.STUDY FUNDING/COMPETING INTEREST(S):This research was supported by The Canadian Institutes of Health Research (MOP 133661 to C.O.), and by RI MUHC-Desjardins Studentship in Child Health Research awarded to M.C.F. The authors have nothing to disclose.