title: Electrophilic aldehyde products of lipid peroxidation selectively adduct to heat shock protein 90 and arylsulfatase A in stallion spermatozoa.
abstract: Oxidative stress is a major determinant of mammalian sperm function stimulating lipid peroxidation cascades that culminate in the generation of potentially cytotoxic aldehydes. The aim of this study was to assess the impact of such aldehydes on the functionality of stallion spermatozoa. The impact of exposure to exogenous acrolein (ACR) and 4-hydroxynonenal (4HNE) was manifested in a highly significant dose- and time-dependent increase in mitochondrial reactive oxygen species (ROS), total cellular ROS, a decrease in sperm motility, and a time-dependent increase in lipid peroxidation. Notably, low doses of ACR and 4HNE also caused a significant decrease in zona binding. In contrast, exogenous malondialdehyde, a commonly used marker of oxidative stress, had little impact on the various sperm parameters assessed. In accounting for the negative physiological impact of ACR and 4HNE, it was noted that both aldehydes readily adducted to sperm proteins located predominantly within the head, proximal centriole, and tail. The detoxifying activity of mitochondrial aldehyde dehydrogenase 2 appeared responsible for a lack of adduction in the midpiece; however, this activity was overwhelmed by 24 h of electrophilic aldehyde exposure. Sequencing of the dominant proteins targeted for ACR and 4HNE covalent modification identified heat shock protein 90 alpha (cytosolic) class A member 1 and arylsulfatase A, respectively. These collective findings may prove useful in the identification of diagnostic biomarkers of stallion fertility and resolving the mechanistic basis of sperm dysfunction in this species.
authors.affiliation: Priority Research Centre for Reproductive Science, Discipline of Biological Sciences, Faculty of Science and Information Technology, University of Newcastle, Callaghan, New South Wales, Australia.|Invasive Animals Cooperative Research Centre, University of Canberra, Bruce, Australian Capital Territory, Australia.
authors.forename: Sally E
authors.initials: SE
authors.lastname: Hall
authors.affiliation: Priority Research Centre for Reproductive Science, Discipline of Biological Sciences, Faculty of Science and Information Technology, University of Newcastle, Callaghan, New South Wales, Australia.|Invasive Animals Cooperative Research Centre, University of Canberra, Bruce, Australian Capital Territory, Australia.
authors.forename: R John
authors.initials: RJ
authors.lastname: Aitken
authors.affiliation: Priority Research Centre for Reproductive Science, Discipline of Biological Sciences, Faculty of Science and Information Technology, University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: Brett
authors.initials: B
authors.lastname: Nixon
authors.affiliation: Analytical and Biomedical Research Facility, Research Division, University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Smith
authors.affiliation: Priority Research Centre for Reproductive Science, Discipline of Biological Sciences, Faculty of Science and Information Technology, University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: Zamira
authors.initials: Z
authors.lastname: Gibb
mesh_terms: D000171:Acrolein; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000378:metabolism*; D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D002553:Cerebroside-Sulfatase / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006736:Horses; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde; D017382:Reactive Oxygen Species / Q000378:metabolism; D013081:Sperm Motility; D013094:Spermatozoa / Q000378:metabolism*; D015044:Zona Pellucida / Q000378:metabolism
chemical_list: D000447:Aldehydes; D018841:HSP90 Heat-Shock Proteins; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D000171:Acrolein; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D002553:Cerebroside-Sulfatase; C027576:4-hydroxy-2-nonenal
keywords: 4-hydroxynonenal; ARSA; HSP90AA1; acrolein; aldehyde dehydrogenase; electrophilic aldehydes; lipid peroxidation; oxidative stress; reactive oxygen species; spermatozoa; stallion