McConnell Josie M L, Petrie Linda
Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen, AB21 9SB, UK.
Reprod Biomed Online. 2004 Oct;9(4):418-24. doi: 10.1016/s1472-6483(10)61277-1.
There is increasing evidence in humans that abnormal mitochondrial DNA (mtDNA) is associated with common degenerative disorders of the twenty-first century. MtDNA is exclusively female in origin and abnormalities in mtDNA can either be inherited, or generated de novo by adverse environmental factors that disturb mitochondrial DNA synthesis or destabilize mtDNA. The preimplantation period of development in mammals was thought to be relatively immune from environmentally induced changes to mtDNA, since no replication of mtDNA was thought to occur at this stage. This study demonstrates that there is a very short period of mtDNA synthesis immediately after fertilization, which can be affected by environmental stress. Adverse culture conditions during this phase of development could therefore alter the mitochondrial genome, with possible long-term consequences for the health of the offspring. The findings have relevance for all assisted reproduction programmes and for the rapidly emerging field of stem cell technologies.
在人类中,越来越多的证据表明,异常线粒体DNA(mtDNA)与21世纪常见的退行性疾病有关。mtDNA完全源自女性,mtDNA异常既可以遗传,也可以由干扰线粒体DNA合成或破坏mtDNA稳定性的不利环境因素重新产生。由于认为在这个阶段不会发生mtDNA复制,所以哺乳动物着床前的发育阶段被认为相对不受环境诱导的mtDNA变化的影响。这项研究表明,受精后立即有一段非常短的mtDNA合成期,这可能会受到环境压力的影响。因此,在发育的这个阶段不利的培养条件可能会改变线粒体基因组,对后代的健康可能产生长期影响。这些发现与所有辅助生殖计划以及迅速兴起的干细胞技术领域都有关系。