Cai Na, Fňašková Monika, Konečná Klára, Fojtová Miloslava, Fajkus Jiří, Coomber Eve, Watt Stephen, Soranzo Nicole, Preiss Marek, Rektor Ivan
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom.
European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, United Kingdom.
Front Genet. 2020 Mar 3;11:87. doi: 10.3389/fgene.2020.00087. eCollection 2020.
Mitochondrial DNA copy number has been previously shown to be elevated with severe and chronic stress, as well as stress-related pathology like Major Depressive Disorder (MDD) and post-traumatic stress disorder (PTSD). While experimental data point to likely recovery of mtDNA copy number changes after the stressful event, time needed for full recovery and whether it can be achieved are still unknown. Further, while it has been shown that stress-related mtDNA elevation affects multiple tissues, its specific consequences for oogenesis and maternal inheritance of mtDNA has never been explored. In this study, we used qPCR to quantify mtDNA copy number in 15 Holocaust survivors and 102 of their second- and third-generation descendants from the Czech Republic, many of whom suffer from PTSD, and compared them to controls in the respective generations. We found no significant difference in mtDNA copy number in the Holocaust survivors compared to controls, whether they have PTSD or not, and no significant elevation in descendants of female Holocaust survivors as compared to descendants of male survivors or controls. Our results showed no evidence of persistence or inheritance of mtDNA changes in Holocaust survivors, though that does not rule out effects in other tissues or mitigating mechanism for such changes.
先前的研究表明,线粒体DNA拷贝数会在遭受严重和慢性应激以及与应激相关的病理学情况(如重度抑郁症(MDD)和创伤后应激障碍(PTSD))时升高。虽然实验数据表明应激事件后线粒体DNA拷贝数变化可能会恢复,但完全恢复所需的时间以及是否能够实现仍不清楚。此外,虽然已经表明与应激相关的线粒体DNA升高会影响多个组织,但从未探讨过其对卵子发生和线粒体DNA母系遗传的具体影响。在本研究中,我们使用qPCR对15名大屠杀幸存者及其来自捷克共和国的102名第二代和第三代后代(其中许多人患有PTSD)的线粒体DNA拷贝数进行了量化,并将他们与各代对照组进行了比较。我们发现,与对照组相比,大屠杀幸存者的线粒体DNA拷贝数没有显著差异,无论他们是否患有PTSD;与男性幸存者或对照组的后代相比,女性大屠杀幸存者的后代中线粒体DNA拷贝数也没有显著升高。我们的结果表明,没有证据表明大屠杀幸存者中线粒体DNA变化会持续或遗传,尽管这并不排除在其他组织中的影响或此类变化的缓解机制。