Increased concentrations of the oxidative DNA adduct 7,8-dihydro-8-oxo-2-deoxyguanosine in the germ-line of men with type 1 diabetes

被引:53
作者
Agbaje, I. M. [1 ]
McVicar, C. M. [1 ]
Schock, B. C. [2 ]
McClure, N. [2 ]
Atkinson, A. B. [3 ]
Rogers, D. [1 ]
Lewis, S. E. M. [1 ]
机构
[1] Queens Univ Belfast, Ctr Clin & Populat Sci, Inst Clin Sci, Reprod Med Res Grp, Belfast BT12 6BJ, Antrim, North Ireland
[2] Queens Univ Belfast, Inst Clin Sci, Div Med & therapeut, Belfast BT12 6BJ, Antrim, North Ireland
[3] Royal Victoria Hosp, Reg Ctr Endicrinol & Diabet, Belfast BT12 6BA, Antrim, North Ireland
关键词
diabetes mellitus; human spermatozoa; 8-hydroxydeoxyguanosine; nuclear DNA; oxidative stress;
D O I
10.1016/S1472-6483(10)60602-5
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
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 I 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 101 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, (r(s) = 0.7, P < 0.05). The genomic damage evident in spermatozoa of type I diabetics may have important implications for their fertility and the outcome of pregnancies fathered by these individuals.
引用
收藏
页码:401 / 409
页数:9
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