title: Advancing age increases sperm chromatin damage and impairs fertility in peroxiredoxin 6 null mice.
abstract: Due to socioeconomic factors, more couples are choosing to delay conception than ever. Increasing average maternal and paternal age in developed countries over the past 40 years has raised the question of how aging affects reproductive success of males and females. Since oxidative stress in the male reproductive tract increases with age, we investigated the impact of advanced paternal age on the integrity of sperm nucleus and reproductive success of males by using a Prdx6(-/-) mouse model. We compared sperm motility, cytoplasmic droplet retention sperm chromatin quality and reproductive outcomes of young (2-month-old), adult (8-month-old), and old (20-month-old) Prdx6(-/-) males with their age-matched wild type (WT) controls. Absence of PRDX6 caused age-dependent impairment of sperm motility and sperm maturation and increased sperm DNA fragmentation and oxidation as well as decreased sperm DNA compaction and protamination. Litter size, total number of litters and total number of pups per male were significantly lower in Prdx6(-/-) males compared to WT controls. These abnormal reproductive outcomes were severely affected by age in Prdx6(-/-) males. In conclusion, the advanced paternal age affects sperm chromatin integrity and fertility more severely in the absence of PRDX6, suggesting a protective role of PRDX6 in age-associated decline in the sperm quality and fertility in mice.
authors: Urology Research Laboratory, Research Institute of the McGill University Health Centre, McGill University, Montréal, Québec, Canada; Department of Surgery (Urology Division), Research Institute of the McGill University Health Centre, McGill University, Montréal, Québec, Canada.
authors: Burak
authors: B
authors: Ozkosem
authors: Institute for Environmental Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors: Sheldon I
authors: SI
authors: Feinstein
authors: Institute for Environmental Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors: Aron B
authors: AB
authors: Fisher
authors: Urology Research Laboratory, Research Institute of the McGill University Health Centre, McGill University, Montréal, Québec, Canada; Department of Surgery (Urology Division), Research Institute of the McGill University Health Centre, McGill University, Montréal, Québec, Canada; Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada. Electronic address: cristian.oflaherty@mcgill.ca.
authors: Cristian
authors: C
authors: O'Flaherty
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000375:Aging; D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D053938:DNA Fragmentation; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis / Q000276:immunology; D005260:Female; D007150:Immunohistochemistry; D007248:Infertility, Male / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress; D054465:Peroxiredoxin VI / Q000172:deficiency / Q000235:genetics*; D013081:Sperm Motility; D013094:Spermatozoa / Q000378:metabolism*
chemical_list: D002843:Chromatin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D054465:Peroxiredoxin VI; D003849:Deoxyguanosine
keywords: Male infertility; Oxidative stress; PRDX6; Paternal age; Reactive oxygen species; Sperm chromatin