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:54
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
相关论文
共 66 条
[41]   Paternal cigarette smoking and the risk of childhood cancer among offspring of nonsmoking mothers [J].
Ji, BT ;
Shu, XO ;
Linet, MS ;
Zheng, W ;
Wacholder, S ;
Gao, YT ;
Ying, DM ;
Jin, F .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1997, 89 (03) :238-244
[42]   Increased oxidative deoxyribonucleic acid damage in the spermatozoa of infertile male patients [J].
Kodama, H ;
Yamaguchi, R ;
Fukuda, J ;
Kasai, H ;
Tanaka, T .
FERTILITY AND STERILITY, 1997, 68 (03) :519-524
[43]   NEW METHOD OF EVALUATING SPERM MORPHOLOGY WITH PREDICTIVE VALUE FOR HUMAN INVITRO FERTILIZATION [J].
KRUGER, TF ;
ACOSTA, AA ;
SIMMONS, KF ;
SWANSON, RJ ;
MATTA, JF ;
VEECK, LL ;
MORSHEDI, M ;
BRUGO, S .
UROLOGY, 1987, 30 (03) :248-251
[44]   Oxidative DNA damage in human sperm influences time to pregnancy [J].
Loft, S ;
Kold-Jensen, T ;
Hjollun, NH ;
Giwercman, A ;
Gyllemborg, J ;
Ernst, E ;
Olsen, J ;
Scheike, T ;
Poulsen, HE ;
Bonde, JP .
HUMAN REPRODUCTION, 2003, 18 (06) :1265-1272
[45]   PRESENCE OF ENDOGENOUS NICKS IN DNA OF EJACULATED HUMAN SPERMATOZOA AND ITS RELATIONSHIP TO CHROMOMYCIN A(3) ACCESSIBILITY [J].
MANICARDI, GC ;
BIANCHI, PG ;
PANTANO, S ;
AZZONI, P ;
BIZZARO, D ;
BIANCHI, U ;
SAKKAS, D .
BIOLOGY OF REPRODUCTION, 1995, 52 (04) :864-867
[46]   X-RAY-INDUCED AND MITOMYCIN-C (MMC)-INDUCED CHROMOSOME-ABERRATIONS IN SPERMIOGENIC GERM-CELLS AND THE REPAIR CAPACITY OF MOUSE EGGS FOR THE X-RAY AND MMC DAMAGE [J].
MATSUDA, Y ;
SEKI, N ;
UTSUGITAKEUCHI, T ;
TOBARI, I .
MUTATION RESEARCH, 1989, 211 (01) :65-75
[47]   REPAIR CAPACITY OF FERTILIZED MOUSE EGGS FOR X-RAY-DAMAGE INDUCED IN SPERM AND MATURE OOCYTES [J].
MATSUDA, Y ;
TOBARI, I .
MUTATION RESEARCH, 1989, 210 (01) :35-47
[48]   Does the increase of 8-hydroxydeoxyguanosine lead to poor sperm quality? [J].
Ni, ZY ;
Liu, YQ ;
Shen, HM ;
Chia, SE ;
Ong, CN .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 1997, 381 (01) :77-82
[49]   Sperm DNA integrity and male infertility [J].
O'Brien, J ;
Zini, A .
UROLOGY, 2005, 65 (01) :16-22
[50]   Evaluating human sperm DNA integrity: relationship between 8-hydroxydeoxyguanosine quantification and the sperm chromatin structure assay [J].
Oger, I ;
Da Cruz, C ;
Panteix, G ;
Menezo, Y .
ZYGOTE, 2003, 11 (04) :367-371