title: Oxidative stress and human spermatozoa: diagnostic and functional significance of aldehydes generated as a result of lipid peroxidation.
abstract: Oxidative stress is known to compromise human sperm function and to activate the intrinsic apoptotic cascade in these cells. One of the key features of oxidatively stressed spermatozoa is the induction of a lipid peroxidation process that results in the formation of aldehydes potentially capable of disrupting sperm function through the formation of adducts with DNA and key proteins. In this study, we have examined the impact of a range of small molecular mass aldehydes generated as a consequence of lipid peroxidation on human sperm function and also compared the two most commonly formed compounds, 4-hydroxynonenal (4HNE) and malondialdehyde (MDA), for their relative ability to reflect a state of oxidative stress in these cells. Dramatic differences in the bioactivity of individual aldehydes were observed, that generally correlated with the second order rate constants describing their interaction with the model nucleophile, glutathione. Our results demonstrate that acrolein and 4HNE were the most reactive lipid aldehydes, inhibiting sperm motility while augmenting reactive oxygen species production, lipid peroxidation, oxidative DNA damage and caspase activation, in a dose-dependent manner (P < 0.001). In contrast, a variety of saturated aldehydes and the well-known marker of oxidative stress, MDA, were without effect on this cell type. While MDA was not cytotoxic per se, its generation did reflect the induction of oxidative stress in vivo and in vitro in a manner that was highly correlated with the bioactive lipid aldehyde, 4HNE. Despite such overall correlations, individual patient samples were observed in which either MDA or 4HNE predominated. Given the relative cytotoxicity of 4HNE, we propose that this aldehyde should be the preferred criterion for diagnosing oxidative stress in the male germ line.
authors.affiliation: Priority Research Centre in Reproductive Science, Discipline of Biological Sciences, Faculty of Science and IT, University of Newcastle, University Drive, Callaghan, New South Wales 2308, Australia Hunter Medical Research Institute (HMRI), Newcastle, New South Wales 2310, Australia CellOxess LLC, 15 Roszel Street, Princeton, NJ 08540, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Moazamian
authors.affiliation: Priority Research Centre in Reproductive Science, Discipline of Biological Sciences, Faculty of Science and IT, University of Newcastle, University Drive, Callaghan, New South Wales 2308, Australia Hunter Medical Research Institute (HMRI), Newcastle, New South Wales 2310, Australia CellOxess LLC, 15 Roszel Street, Princeton, NJ 08540, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Polhemus
authors.affiliation: Priority Research Centre in Reproductive Science, Discipline of Biological Sciences, Faculty of Science and IT, University of Newcastle, University Drive, Callaghan, New South Wales 2308, Australia Hunter Medical Research Institute (HMRI), Newcastle, New South Wales 2310, Australia.
authors.forename: Haley
authors.initials: H
authors.lastname: Connaughton
authors.affiliation: Priority Research Centre in Reproductive Science, Discipline of Biological Sciences, Faculty of Science and IT, University of Newcastle, University Drive, Callaghan, New South Wales 2308, Australia Hunter Medical Research Institute (HMRI), Newcastle, New South Wales 2310, Australia.
authors.forename: Barbara
authors.initials: B
authors.lastname: Fraser
authors.affiliation: Priority Research Centre in Reproductive Science, Discipline of Biological Sciences, Faculty of Science and IT, University of Newcastle, University Drive, Callaghan, New South Wales 2308, Australia Hunter Medical Research Institute (HMRI), Newcastle, New South Wales 2310, Australia.
authors.forename: Sara
authors.initials: S
authors.lastname: Whiting
authors.affiliation: CellOxess LLC, 15 Roszel Street, Princeton, NJ 08540, USA.
authors.forename: Parviz
authors.initials: P
authors.lastname: Gharagozloo
authors.affiliation: Priority Research Centre in Reproductive Science, Discipline of Biological Sciences, Faculty of Science and IT, University of Newcastle, University Drive, Callaghan, New South Wales 2308, Australia Hunter Medical Research Institute (HMRI), Newcastle, New South Wales 2310, Australia CellOxess LLC, 15 Roszel Street, Princeton, NJ 08540, USA john.aitken@newcastle.edu.au.
authors.forename: Robert John
authors.initials: RJ
authors.lastname: Aitken
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D017209:Apoptosis; D004249:DNA Damage; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013081:Sperm Motility; D013094:Spermatozoa / Q000378:metabolism* / Q000502:physiology
chemical_list: D000447:Aldehydes; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; C027576:4-hydroxy-2-nonenal
keywords: human spermatozoa; lipid aldehydes; lipid peroxidation; oxidative stress