Increased concentrations of the oxidative DNA adduct 7,8-dihydro-8-oxo-2-deoxyguanosine in the germ-line of men with type 1 diabetes.
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.
Agbaje
I M
IM
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
McVicar
C M
CM
Schock
B C
BC
McClure
N
N
Atkinson
A B
AB
Rogers
D
D
Lewis
S E M
SE
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*
D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine