title: Increased concentrations of the oxidative DNA adduct 7,8-dihydro-8-oxo-2-deoxyguanosine in the germ-line of men with type 1 diabetes.
abstract: The effects of diabetes mellitus on male reproductive health have not been clearly defined. A previous publication from this group reported significantly higher levels of nuclear DNA fragmentation and mitochondrial DNA deletions in spermatozoa from men with type 1 diabetes. This study compared semen profiles, sperm DNA fragmentation and levels of oxidative DNA modification in spermatozoa of diabetic and non-diabetic men. Semen samples from 12 non-diabetic, fertile men and 11 type 1 diabetics were obtained and subjected to conventional light microscopic semen analysis. Nuclear DNA fragmentation was assessed using an alkaline Comet assay and concentrations of 7,8-dihydro-8-oxo-2-deoxyguanosine (8-OHdG), an oxidative adduct of the purine guanosine, were assessed by high-performance liquid chromatography. Conventional semen profiles were similar in both groups, whilst spermatozoa from type 1 diabetics showed significantly higher levels of DNA fragmentation (44% versus 27%; P < 0.05) and concentrations of 8-OHdG (3.6 versus 2.0 molecules of 8-OHdG per 10(5) molecules of deoxyguanosine; P < 0.05). Furthermore, a positive correlation was observed between DNA fragmentation and concentrations of 8-OHdG per 10(5) molecules of deoxyguanosine (rs = 0.7, P < 0.05). The genomic damage evident in spermatozoa of type 1 diabetics may have important implications for their fertility and the outcome of pregnancies fathered by these individuals.
authors.affiliation: Reproductive Medicine Research Group, Centre for Clinical and Population Sciences, Queen's University, Belfast, Institute of Clinical Science, Grosvenor Road, Belfast BT12 6BJ, UK. i.agbaje@qub.ac.uk
authors.forename: I M
authors.initials: IM
authors.lastname: Agbaje
authors.forename: C M
authors.initials: CM
authors.lastname: McVicar
authors.forename: B C
authors.initials: BC
authors.lastname: Schock
authors.forename: N
authors.initials: N
authors.lastname: McClure
authors.forename: A B
authors.initials: AB
authors.lastname: Atkinson
authors.forename: D
authors.initials: D
authors.lastname: Rogers
authors.forename: S E M
authors.initials: SE
authors.lastname: Lewis
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D016022:Case-Control Studies; D053938:DNA Fragmentation; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D006801:Humans; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D012661:Semen / Q000166:cytology; D013094:Spermatozoa / Q000378:metabolism*
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine