Levels of cell-free DNA and DNAse I activity in complicated and normal pregnancies

Avetisova KG1, Kostyuk SV2, Kostyuk EV2, Ershova ES2, Shmarina GV2, Veiko NN2, Spiridonov DS1, Klimenko PA1, Kurtser MA1
About authors

1 Department of Obstetrics and Gynecology, Faculty of Pediatrics,
Pirogov Russian National Research Medical University, Moscow

2 Laboratory of Molecular Biology, Research Centre for Medical Genetics, Moscow

Correspondence should be addressed: Kristina G. Avetisova
Sevastopol avenue, 24a, Moscow, 117209; ur.xednay@6102avositeva.c

Received: 2018-03-15 Accepted: 2018-06-27 Published online: 2018-09-15

 Placental pathology is accompanied by the activation of apoptosis in the trophoblast and the subsequent increase in the concentrations of microvesicles containing placental (or fetal) DNA accumulating in the maternal blood. Fragments of fetal DNA stimulate the release of nuclear and/or mitochondrial DNA fragments by neutrophils. Therefore, one can expect that complicated pregnancies will be characterized by the dramatic elevation of total cell-free DNA (cfDNA) levels in maternal plasma. The aim of this work was to study the dynamics of plasma cfDNA concentrations and the activity of DNase I, an enzyme involved in the elimination of cfDNA from the bloodstream, in nonpregnant and pregnant women. Our study recruited 40 healthy nonpregnant women, 40 women with uncomplicated pregnancies and 35 women with the intrauterine growth restriction (IUGR) of the fetus. We did not observe the elevation of the total cfDNA concentrations in the patients with complicated pregnancies. Moreover, cfDNA concentrations in their plasma were even lower (though this difference was statistically insignificant) than in healthy pregnant and nonpregnant women. The median values of cfDNA concentrations in the group of healthy nonpregnant women were 75.5 ng/ml; in the group of healthy pregnant women, 78.0 ng/ml; and in the patients with IUGR, it was 42.1 ng/ml. At the same time, we observed a significant increase in DNase I activity in the plasma of women with IUGR. The median DNase I activity in the groups of healthy pregnant and nonpregnant women was 3.0 and 3.4 IU/ml, respectively. In patients with different grades IUGR of the fetus this parameter was as high as 6.3 IU/ml (р < 0.001). Increased DNase I activity in the plasma of women with complicated pregnancies indirectly suggests a transient elevation of circulating cfDNA levels. Our study shows that the high level of activity exhibited by the cfDNA elimination system impedes the analysis of cfDNA concentrations in complicated pregnancies and skews its results. However, if cfDNA, DNase I activity and cfDNA/DNase I ratio were all taken into account, it could be possible to develop a tool for the monitoring of cell death in the mother throughout the entire pregnancy.

Keywords: preeclampsia, pregnancy, cfDNA, DNase I, IUGR