Possibilities of predicting preterm birth using mitochondrial DNA and VDAC1 protein


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Abstract

Objective. To study the prognostic role of determining the content of mitochondrial DNA in the blood and voltage-dependent anion channel 1 (VDAC1) in the placenta during preterm birth. Materials and methods. The study included 142 pregnant women. They were divided into three groups: group 1 consisted of 43 patients who had a spontaneous preterm birth; group 2 included 47 women who had a preterm birth and premature rupture of membranes (PROM) and group 3 consisted of 52 women who had threatened preterm labor followed by term birth. The quantitative assessment of mtDNA copy number in peripheral blood plasma (reverse transcription quantitative real-time PCR (RT-qPCR)) as well as determining the level of VDAC1 in the placenta were carried out using western blotting. Results. The study of the VDAC1 protein content in the placenta showed its statistically significantly high content in patients who had a preterm birth and PROM at 22-27 6/7 and 28-33 6/7 weeks’ gestation compared to the patients who had a term birth and a spontaneous preterm birth at 22-27 6/7 weeks’ gestation (p<0.05). Patients with normal pregnancy showed an increase in the level of mtDNA in the peripheral blood plasma with the gestational age, reaching the maximum values by 37-40 weeks. Patients who had preterm labor with PROM showed significantly higher mtDNA levels at 22-27 6/7 and 28-33 6/7 weeks than those who had a normal pregnancy, but it was lower than in patients with term birth. In case of spontaneous preterm birth, the level of mtDNA at 22-27 6/7 and 34-36 6/7 weeks’ gestation was statistically significantly higher, compared with one in normal pregnancy and term birth. Determining the level of mtDNA copy number using ROC analysis with high sensitivity (77%) and specificity (93%) makes it possible to predict the risk of preterm birth. Conclusion. Statistically significant differences in the content of VDAC1 protein in the placenta and the level of mtDNA copy number in the peripheral blood plasma in spontaneous preterm birth and in preterm birth with PROM in contrast to the normal course of pregnancy suggest that they contribute to the development of these complications of pregnancy. The identification of these markers can facilitate timely diagnosis and initiation of personalized complex therapy aimed at prolonging pregnancy.

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About the authors

Victor L. Tyutyunnik

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; Perinatal Center, European Medical Center

Email: tioutiounnik@mail.ru
professor, M.D., Ph.D., Leading Researcher of Research and Development Service

Natalia E. Kan

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: kan-med@mail.ru
professor, M.D., Ph.D., Deputy Director of Science

Mikhail Yu. Vysokikh

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: m_vysokikh@oparina4.ru
Ph.D., Head of Mitochondrial Medicine Research Group

Diana N. Kokoeva

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: dikokoeva@mail.ru
postgraduate student

Andrey E. Donnikov

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: donnikov@dna-technology.ru
Ph.D., Head of the Laboratory of Molecular Genetic Methods

Alena G. Saribekova

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: a_aruschanova@oparina4.ru
postgraduate student

Marzhanat K. Medzhidova

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: marzhana-m@yandex.ru
Ph,D., doctoral student

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