Mitochondria have their own circular multi-copy genome (mtDNA), and abnormalities in the copy number are implicated in mitochondrial dysfunction, which contributes to a variety of aging-related pathologies. However, not much is known about the genetic correlation of mtDNA copy number across multiple generations and its physiological significance. We measured the mtDNA copy number in cord blood or peripheral blood from 149 three-generation families, specifically the newborns, parents, and grandparents, of 149 families, totaling 1041 individuals. All of the biological specimens and information were provided by the Tohoku Medical Megabank Project in Japan. We also analyzed their maternal factors during pregnancy and neonatal outcomes. While the maternal peripheral blood mtDNA copy number was lower than that of other adult family members, it was negatively correlated with cord blood mtDNA copy number in male infants. Also, cord blood mtDNA copy numbers were negatively correlated with perinatal outcomes, such as gestation age, birth weight, and umbilical cord length, for both male and female neonates. Furthermore, the mtDNA copy number in the infants born to mothers who took folic acid supplements during pregnancy would be lower than in the infants born to mothers who did not take them. This data-driven study offers the most comprehensive view to date on the genetic and physiological significance of mtDNA copy number in cord blood or peripheral blood taken from three generations, totaling more than 1000 individuals. Our findings indicate that mtDNA copy number would be one of the transgenerational biomarkers for assessing perinatal outcomes, as well as that appropriate medical interventions could improve the outcomes via quantitative changes in mtDNA.

中文翻译：

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三代间线粒体 DNA 拷贝数变异：评估围产期结局的可能生物标志物


线粒体有自己的环状多拷贝基因组（mtDNA），拷贝数异常与线粒体功能障碍有关，从而导致多种与衰老相关的病理。然而，人们对多代线粒体DNA拷贝数的遗传相关性及其生理意义知之甚少。我们测量了149个三代家庭的脐带血或外周血中的线粒体DNA拷贝数，特别是149个家庭的新生儿、父母和祖父母，共计1041人。所有生物标本和信息均由日本东北医疗大银行项目提供。我们还分析了她们怀孕期间的母亲因素和新生儿结局。虽然母亲外周血mtDNA拷贝数低于其他成年家庭成员，但与男婴脐带血mtDNA拷贝数呈负相关。此外，对于男性和女性新生儿来说，脐带血线粒体 DNA 拷贝数与围产期结局呈负相关，例如孕龄、出生体重和脐带长度。此外，在怀孕期间服用叶酸补充剂的母亲所生的婴儿的线粒体DNA拷贝数会低于未服用叶酸补充剂的母亲所生的婴儿。这项数据驱动的研究提供了迄今为止最全面的观点，了解来自三代（总计超过 1000 人）的脐带血或外周血中 mtDNA 拷贝数的遗传和生理意义。我们的研究结果表明，线粒体DNA拷贝数将成为评估围产期结局的跨代生物标志物之一，并且适当的医疗干预措施可以通过线粒体DNA的数量变化来改善结局。