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 compa...

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Published in:Reproductive biomedicine online 2008, Vol.16 (3), p.401-409
Main Authors: Agbaje, IM, McVicar, CM, Schock, BC, McClure, N, Atkinson, AB, Rogers, D, Lewise, SEM
Format: Article
Language:English
Subjects:
8-hydroxydeoxyguanosine
Case-Control Studies
Deoxyguanosine - analogs & derivatives
Deoxyguanosine - metabolism
diabetes mellitus
Diabetes Mellitus, Type 1 - metabolism
DNA Fragmentation
human spermatozoa
Humans
Male
nuclear DNA
Obstetrics and Gynecology
oxidative stress
Oxidative Stress - physiology
Semen - cytology
Spermatozoa - metabolism
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Summary: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 105 molecules of deoxyguanosine; P < 0.05). Furthermore, a positive correlation was observed between DNA fragmentation and concentrations of 8-OHdG per 105 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.
ISSN:1472-6483
1472-6491
DOI:10.1016/S1472-6483(10)60602-5