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1型糖尿病男性生殖细胞中氧化性DNA加合物7,8-二氢-8-氧代-2'-脱氧鸟苷的浓度升高。

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

作者信息

Agbaje I M, McVicar C M, Schock B C, McClure N, Atkinson A B, Rogers D, Lewis S E M

机构信息

Reproductive Medicine Research Group, Centre for Clinical and Population Sciences, Queen's University, Belfast, Institute of Clinical Science, Grosvenor Road, Belfast BT12 6BJ, UK.

出版信息

Reprod Biomed Online. 2008 Mar;16(3):401-9. doi: 10.1016/s1472-6483(10)60602-5.

DOI:10.1016/s1472-6483(10)60602-5
PMID:18339265
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.

摘要

糖尿病对男性生殖健康的影响尚未明确界定。该研究团队之前发表的一篇论文报告称,1型糖尿病男性精子中的核DNA片段化水平和线粒体DNA缺失率显著更高。本研究比较了糖尿病男性和非糖尿病男性精子的精液参数、精子DNA片段化情况以及氧化性DNA修饰水平。收集了12名非糖尿病可育男性和11名1型糖尿病男性的精液样本,并进行传统光学显微镜精液分析。使用碱性彗星试验评估核DNA片段化情况,通过高效液相色谱法评估嘌呤鸟苷的氧化性加合物7,8-二氢-8-氧代-2'-脱氧鸟苷(8-OHdG)的浓度。两组的传统精液参数相似,而1型糖尿病男性的精子显示出显著更高的DNA片段化水平(44%对27%;P<0.05)和8-OHdG浓度(每10⁵个脱氧鸟苷分子中有3.6个8-OHdG分子对2.0个;P<0.05)。此外,观察到DNA片段化与每10⁵个脱氧鸟苷分子的8-OHdG浓度之间存在正相关(rs = 0.7,P<0.05)。1型糖尿病男性精子中明显的基因组损伤可能对其生育能力以及这些个体生育的妊娠结局具有重要影响。

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