title: Incomplete protection of genetic integrity of mature spermatozoa against oxidative stress.
abstract: Although DNA damage in human spermatozoa is associated with adverse health effects, its origin is not fully understood. Therefore, we assessed biomarkers in ejaculates that retrospectively reflect processes that occurred in the epididymis or testis. Smoking increased the amount of DNA strand breaks (P<0.01), and enhanced the presence of vitamin C radicals in seminal plasma. In vitro, vitamin C protected mature spermatozoa against DNA damage, but this protection appeared to be insufficient in vivo. CAT and DDIT4 expression in spermatozoa were higher in smokers than in nonsmokers, but were not related to DNA damage. CAT and DDIT4 expression were inversely related with sperm count (P=0.039 and 0.024 resp.), but no effect was observed for SOD2 expression. These data indicate that spermatozoa of smokers encounter higher levels of oxidative stress. Expression of antioxidant enzymes and seminal vitamin C were insufficient to provide full protection of spermatozoa against DNA damage.
authors.affiliation: Department of Toxicology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Joost O
authors.initials: JO
authors.lastname: Linschooten
authors.forename: Julian
authors.initials: J
authors.lastname: Laubenthal
authors.forename: Eduardo
authors.initials: E
authors.lastname: Cemeli
authors.forename: Adolf
authors.initials: A
authors.lastname: Baumgartner
authors.forename: Diana
authors.initials: D
authors.lastname: Anderson
authors.forename: Ville E
authors.initials: VE
authors.lastname: Sipinen
authors.forename: Gunnar
authors.initials: G
authors.lastname: Brunborg
authors.forename: Guido R M M
authors.initials: GR
authors.lastname: Haenen
authors.forename: Eleni
authors.initials: E
authors.lastname: Fthenou
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Briedé
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: van Schooten
authors.forename: Roger W L
authors.initials: RW
authors.lastname: Godschalk
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D020552:Comet Assay; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004347:Drug Interactions; D005609:Free Radicals / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D008297:Male; D009845:Oligospermia / Q000209:etiology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012661:Semen / Q000187:drug effects / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*; D013094:Spermatozoa / Q000166:cytology / Q000187:drug effects*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; C469991:DDIT4 protein, human; D005609:Free Radicals; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D004247:DNA; D006861:Hydrogen Peroxide; D002374:Catalase; D001205:Ascorbic Acid