Transgenerational changes in somatic and germ line genetic integrity of first-generation offspring derived from the DNA damaged sperm
Transgenerational changes in somatic and germ line genetic integrity of first-generation offspring derived from the DNA damaged sperm
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DOI：
10.1016/j.fertnstert.2009.06.015
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发表时间：
2010-05-15
影响因子：
6.7
通讯作者：
Kumar, Pratap
中科院分区：
文献类型：
--
作者：
Adiga, Satish Kumar;Upadhya, Dinesh;Kumar, Pratap
目的：为了报告一种更定量的方法来研究不同水平的精子DNA损伤对小鼠模型中基因组不稳定性的跨代变化的影响。设计：实验性前瞻性研究。设置：胚胎学研究实验室。动物：瑞士白化病小鼠。干预：通过不同剂量的g-辐射诱导雄性小鼠的精子DNA损伤，然后与健康雌性小鼠交配。主要结果测量：胚胎，胎儿和精子的基因组完整性的F1小鼠来自DNA损伤的sperm. Results（S）：遗传完整性的跨代变化归因于剂量依赖性增加的微核的频率在植入前胚胎和伴随的增加，在胎儿肝细胞和精子染色质修饰的基因组不稳定性在F1雄性。精子DNA损伤的程度和体细胞和生殖系基因组instability. Conclusions（S）：精子介导的跨代基因组不稳定性之间存在着很强的正相关性，这取决于在受精时存在于父系精子的DNA损伤量。（Fertil Steril（R）2010; 93：2486-90. (C)美国生殖医学会（American Society for Reproductive Medicine）
Objective: To report a more quantitative approach to study the influence of varying levels of sperm DNA damage on transgenerational changes in genomic instability in a mouse model.Design: Experimental prospective study.Setting: Embryology research laboratory.Animal(s): Swiss albino mice.Intervention(s): The sperm DNA damage was induced by different doses of g-irradiation to male mice followed by mating with healthy female mice.Main Outcome Measure(s): Genomic integrity in embryos, fetus, and spermatozoa of F1 mice derived from the DNA-damaged sperm.Result(s): The transgenerational changes in genetic integrity were attributed by a dose-dependent increase in the frequency of micronuclei in preimplantation embryos and a concomitant increase in genomic instability in fetal liver cells and sperm chromatin modifications in F1 males. A strong positive correlation was observed between the extent of sperm DNA damage and somatic and germ-line genomic instability.Conclusion(s): Sperm-mediated transgenerational genomic instability is dependent on the amount of DNA damage present in the sire's sperm at the time of fertilization. (Fertil Steril (R) 2010; 93: 2486-90. (C) 2010 by American Society for Reproductive Medicine.)