Limberg A S, Berg F, Köper E, Lindgraf C, Gevers C, Kumsta R, Hummel E M, Moser D A
Department of Genetic Psychology, Faculty of Psychology, Ruhr-University Bochum, Universitätsstraße 150, Bochum, Germany.
Department of Behavioural and Cognitive Sciences, Laboratory for Stress and Gene-Environment Interplay, University of Luxemburg, Porte des Sciences, Esch-sur-Alzette, Luxembourg.
Transl Psychiatry. 2025 Jan 25;15(1):26. doi: 10.1038/s41398-025-03242-5.
Cell-free DNA (cfDNA) is continuously shed by all cells in the body, but the regulation of this process and its physiological functions are still largely unknown. Previous research has demonstrated that both nuclear (cf-nDNA) and mitochondrial (cf-mtDNA) cfDNA levels increase in plasma in response to acute psychosocial and physical stress in males. This study further investigated these findings by testing 31 female participants (16 using oral hormonal contraception and 15 not using oral hormonal contraception), and the results were subsequently compared with those of 16 male participants. In addition, cf-nDNA and cf-mtDNA were comparatively quantified in both plasma and saliva at four time points, 2 min before and 2, 15, and 45 min after stress induction. A novel method was implemented to facilitate the straightforward collection of capillary blood by non-medical personnel for plasma analysis. While cf-mtDNA is readily detectable in body fluids due to its high copy number, the quantification of cf-nDNA is challenging due to its low abundance. To overcome this, a multiplex quantitative polymerase chain reaction (qPCR) protocol targeting L1PA2 elements, which are prevalent in the human genome, was utilized. The analysis indicated significantly elevated levels of cf-nDNA in both plasma and saliva in all participants, irrespective of gender, following psychosocial and physical stress. Conversely, neither plasma nor saliva exhibited a consistent or stress-induced release pattern for cf-mtDNA. CfDNA is a promising biomarker that is consistently released after stress in both men and women and can be detected in both plasma and saliva. However, further research is necessary to elucidate the mechanisms of cfDNA release from specific cells and to understand its biological function in the body.
游离DNA（cfDNA）由体内所有细胞持续释放，但其释放过程的调控及其生理功能仍大多未知。先前的研究表明，在男性中，应对急性心理社会和身体压力时，血浆中的核游离DNA（cf-nDNA）和线粒体游离DNA（cf-mtDNA）水平都会升高。本研究通过对31名女性参与者（16名使用口服激素避孕药，15名未使用口服激素避孕药）进行测试，进一步探究了这些发现，随后将结果与16名男性参与者的结果进行了比较。此外，在应激诱导前2分钟以及诱导后2、15和45分钟这四个时间点，对血浆和唾液中的cf-nDNA和cf-mtDNA进行了相对定量。实施了一种新方法，以方便非医务人员直接采集毛细血管血用于血浆分析。虽然cf-mtDNA因其高拷贝数在体液中易于检测，但由于cf-nDNA丰度低，其定量具有挑战性。为克服这一问题，采用了一种针对人类基因组中普遍存在的L1PA2元件的多重定量聚合酶链反应（qPCR）方案。分析表明，在心理社会和身体应激后，所有参与者（无论性别）的血浆和唾液中cf-nDNA水平均显著升高。相反，血浆和唾液中cf-mtDNA均未表现出一致的或应激诱导的释放模式。CfDNA是一种很有前景的生物标志物，在男性和女性应激后都会持续释放，并且可以在血浆和唾液中检测到。然而，有必要进一步研究以阐明cfDNA从特定细胞释放的机制，并了解其在体内的生物学功能。
