title: Absence of Peroxiredoxin 6 Amplifies the Effect of Oxidant Stress on Mobility and SCSA/CMA3 Defined Chromatin Quality and Impairs Fertilizing Ability of Mouse Spermatozoa.
abstract: Oxidative stress, the imbalance between reactive oxygen species production and antioxidant defenses, is associated with male infertility. Peroxiredoxins (PRDXs) are antioxidant enzymes with a wide distribution in spermatozoa. PRDX6 is highly abundant and located in all subcellular compartments of the spermatozoon. Infertile men have lower levels of sperm PRDX6 associated with low sperm motility and high DNA damage. In order to better understand the role of PRDX6 in male reproduction, the aim of this study was to elucidate the impact of the lack of PRDX6 on male mouse fertility. Spermatozoa lacking PRDX6 showed significantly increased levels of cellular oxidative damage evidenced by high levels of lipid peroxidation, 8-hydroxy-deoxyguanosine (DNA oxidation), and protein oxidation (S-glutathionylation and carbonylation), lower sperm chromatin quality (high DNA fragmentation and low DNA compaction, due to low levels of protamination and a high percentage of free thiols), along with decreased sperm motility and impairment of capacitation as compared with wild-type (WT) spermatozoa. These manifestations of damage are exacerbated by tert-butyl hydroperoxide treatment in vivo. While WT males partially recovered the quality of their spermatozoa (in terms of motility and sperm DNA integrity), Prdx6(-/-) males showed higher levels of sperm damage (lower motility and chromatin integrity) 6 mo after the end of treatment. In conclusion, Prdx6(-/-) males are more vulnerable to oxidative stress than WT males, resulting in impairment of sperm quality and ability to fertilize the oocyte, compatible with the subfertility phenotype observed in these knockout mice.
authors.affiliation: Urology Research Laboratory, Research Institute of the McGill University Health Centre, McGill University, Montréal, Québec, Canada Department of Surgery (Urology Division), McGill University, Montréal, Québec, Canada.
authors.forename: Burak
authors.initials: B
authors.lastname: Ozkosem
authors.affiliation: Institute for Environmental Medicine, Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Sheldon I
authors.initials: SI
authors.lastname: Feinstein
authors.affiliation: Institute for Environmental Medicine, Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Aron B
authors.initials: AB
authors.lastname: Fisher
authors.affiliation: Urology Research Laboratory, Research Institute of the McGill University Health Centre, McGill University, Montréal, Québec, Canada Department of Surgery (Urology Division), McGill University, Montréal, Québec, Canada Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada cristian.oflaherty@mcgill.ca.
authors.forename: Cristian
authors.initials: C
authors.lastname: O'Flaherty
mesh_terms: D000818:Animals; D002843:Chromatin; D014128:Chromomycin A3 / Q000494:pharmacology; D005306:Fertilization / Q000502:physiology; D005456:Fluorescent Dyes / Q000494:pharmacology; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress; D054465:Peroxiredoxin VI / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D055101:Semen Analysis; D013081:Sperm Motility / Q000502:physiology*; D013094:Spermatozoa / Q000502:physiology*
chemical_list: D002843:Chromatin; D005456:Fluorescent Dyes; D014128:Chromomycin A3; D054465:Peroxiredoxin VI; C515983:Prdx6 protein, mouse
keywords: chromomycin A3; fertility; gamete biology; male infertility; oxidative stress; reactive oxygen species; sperm DNA fragmentation; sperm capacitation; sperm chromatin structure assay; sperm function