Mitochondrial proteins of peripheral plasma microvesicles as triggers of aseptic inflammatory responses in women with threatened, recurrent abortion and physiological pregnancy

Bulatova Yu.S., Tetruashvili N.K., Vishnyakova P.A., Vysokikh M.Yu., Marei M.V., Bobrov M.Yu., Pyataeva S.V.

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, Moscow 117997, Ac. Oparina str. 4, Russia
The paper presents the results of a pilot study conducted to determine proinflammatory factors, such as mitochondrial damage-associated molecular patterns (mtDMAPs), in pregnant women with threatened, recurrent abortion and a physiological gestational process.
Objective. To determine the peripheral blood levels of the proinflammatory factors mtDMAPs in patients with threatened and recurrent abortion, whose pregnancies were prolonged with drug therapy versus the similar indicators in women with physiological pregnancy and non-developing pregnancy at 6-12 weeks.
Subjects and methods. The investigation enrolled 37 pregnant women, including 15 with recurrent abortion, 10 with threatened abortion, and 12 with physiological pregnancy. To determine the levels of the proinflammatory factors mtDMAPs, the patients’ venous blood was fractionated; microvesicles were isolated from the obtained plasma, and the content of mitochondrial proteins was analyzed by Western blot. An ANOVA was used to statistically process the findings in accordance with the SPSS Statistics.
Results. A comparative analysis showed that women with threatened and recurrent abortion, whose pregnancy was successfully prolonged with therapy, had a synchronous drop in the level of the mitochondrial outer membrane protein, voltage-dependent anion channel 1 (VDAC1), which was present in peripheral blood as part of microvesicles with a longer gestation period. In cases of non-developing pregnancy, there was a sharp increase in the levels of the protein VDAC1 at 9-12 weeks’ gestation, which was significantly different from the cases of pregnancy at term. The threatened miscarriage group showed an abnormally high level of this protein within the first 6 weeks and therapy-induced normalization of its content at 9-12 weeks to low values inherent in physiological pregnancy. Analysis of the distribution of the protein TFAM showed no significant differences between the groups of patients with term pregnancy for the same gestation periods, whereas the non-developing pregnancy group displayed a significant (approximate double) drop in the amount of TFAM despite ongoing therapy.
Conclusion. The determination of the levels of mtDAMPs will be able to early predict adverse pregnancy outcome in women with recurrent abortion and to evaluate the efficiency of therapy for this disease.

Keywords

recurrent abortion
threatened abortion
non-developing pregnancy
recurrent miscarriage
mitochondrial proteins
proinflammatory factors
plasma microvesicles
inflammation

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Received 09.06.2017

Accepted 23.06.2017

About the Authors

Bulatova Yulia S., Graduate student, Department of Pregnancy Loss Prevention and Therapy, Research Center of Obstetrics, Gynecology and Perinatology,
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954381477. E-mail: yu.bulatova@mail.ru
Тetruashvili Nana K., Doctor of Medicine, Head of the Department of Pregnancy Loss Prevention and Therapy, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954381477. E-mail: tetrauly@mail.ru
Vishnyakova P.A., researcher at the Laboratory of mitochondrial medicine, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: vpa2002@mail.ru
Vysokikh Mikhail Y., PhD, the head of mitochondrial medicine research group, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954387633, ext. 1472. E-mail: m_vysokikh@oparina4.ru
Marey M.V., researcher at the Laboratory of mitochondrial medicine, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: m_marey@oparina4.ru
Pyataeva S.V., PhD., researcher at mitochondrial medicine research group, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: biosonya@gmail.com

For citations: Bulatova Yu.S., Tetruashvili N.K., Vishnyakova P.A., Vysokikh M.Yu., Marei M.V., Bobrov M.Yu., Pyataeva S.V. Mitochondrial proteins of peripheral plasma microvesicles as triggers of aseptic inflammatory responses in women with threatened, recurrent abortion and physiological pregnancy. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2018; (4): 42-8. (in Russian)
https://dx.doi.org/10.18565/aig.2018.4.42-48

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