Increased mitochondrial and ribosomal DNA copy numbers in cell-free DNA samples obtained from women with complicated pregnancies - 11th International Symposium on Circulating Nucleic Acids in Plasma and Serum (CNAPS)

Anastasiia Poletkina ¹ Svetlana Kostyuk ^1,2 Natalia Veiko ¹ Elisaveta Ershova ^1,2 Petr Klimenko ³ Kristina Avetisova ³ Edmund Kostyuk ⁴ Galina Shmarina ^1,2,5

¹Laboratory of Molecular Biology, Research Centre for Medical Genetics (RCMG), Moscow, Russia
²., I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
³Pediatric Faculty, Pirogov Russian National Research Medical University, Moscow, Russia
⁴., Center of Family Planning and Reproduction, Moscow, Russia
⁵., G.N. Gabrichevsky Institute of Epidemiology and Microbiology, Moscow, Moscow, Russia

Circulating cell-free nucleic acids in plasma and serum are novel biomarkers with promising clinical applications in different medical fields, including prenatal screening and various forms of pregnancy complications. The aim of the study was to investigate plasma cell-free (cf)DNA characteristics in unaffected and complicated pregnancies.

The study included 49 pregnant females with hypertensive disorders during their third trimester (20 with mild-to-moderate preeclampsia) and 31 normotensive pregnant women. Cell-free DNA (cfDNA) was isolated from plasma using phenol extraction and quantified by Hoechst 33528 fluorescence. 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels as well as mitochondrial DNA (mtDNA) and ribosomal DNA (rbDNA) copy numbers in cfDNA samples were determined by non-radioactive quantitative dot hybridization.

Circulating cfDNA levels were significantly elevated in pregnancies complicated with hypertensive disorders: 1133.5±321.2 vs 387.6±69.0 ng/ml in control group (p < 0.002). In addition, for the females with complicated pregnancies 4-fold increase in mtDNA copy numbers and 1.5-fold increase in rbDNA copy numbers in cfDNA samples had been found (550.4±74.1 vs 140.8±23.2 arb.units and 1516.1±49.7 vs 947.9±91.7 arb.units, respectively, both p<0.0001). In the same time there were no significant differences between 8-OHdG levels in cfDNA samples of hypertensive and normotensive pregnant women (267.8±107.2 vs 47.1±12.7, p=0,315). It has been noted that a significant positive Spearman correlation between plasma cfDNA concentrations, mtDNA copy numbers, rbDNA copy numbers and clinical parameters including systolic and diastolic blood pressure as well as albuminuria degree had been found.

In conclusion, elevated mtDNA and rbDNA copy numbers was observed in plasma cfDNA samples from pregnant women with hypertensive disorders. The pathophysiological significance of this finding awaits further studies.

The study was supported by RFBR grant № 17-29-06017ofi_m.