Mitochondrial proteins of peripheral plasma microvesicles as biomarkers of early pregnancy losses

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

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 on the determination of proinflammatory factors of mitochondrial damage-associated molecular patterns (mtDAMP) in pregnant women with physiological pregnancy and recurrent early miscarriages.
Objective. To determine the levels of proinflammatory factors of mtDAMP in the peripheral blood of patients with threatened and recurrent miscarriage versus the similar indicators in women with physiological pregnancy.
Subjects and methods. The investigation enrolled 24 pregnant women whose peripheral plasma samples were selected retrospectively after successful achievement of 22 weeks’ gestation in 12 patients (a control group) and in 12 patients with recurrent early miscarriage (a study group). To determine the level of mtDAMP proteins in the patients of the examined groups, their venous blood was fractionated, microvesicles were isolated from the obtained plasma, and mitochondrial protein levels were analyzed by Western-blotting. The findings were statistically processed using the SPSS program according to the ANOVA method.
Results. Comparative analysis of the relative content of mitochondrial proteins in the plasma microvesicles showed that in the women with threatened and recurrent miscarriage, whose pregnancy spontaneously aborted, the levels of all marker proteins were significantly lower than those in the women of the control group (p < 0.01).
Conclusion. The low levels of proinflammatory factors of peripheral plasma mtDAMP are shown to be an unfavorable factor for early pregnancy.

Keywords

recurrent miscarriage
pregnancy
mitochondria
proinflammatory factors
mitochondrial proteins
inflammation

Supplementary Materials

  1. Fig. 1. Typical electrophoretogram and Western blot of microvesicles of plasma of peripheral blood of women of the studied groups. Coloring with monoclonal antibodies to porin protein (VDAC1). M - a marker of molecular weight, the arrow indicates the position of the marker 34kDa, H - the norm, B - the habitual miscarriage
  2. Fig. 2. Level of relative expression of mitochondrial proteins in blood plasma microvysicles. White - the norm, black - miscarriage. A - Porin (VDAC1), B - mtDNA translation initiation protein (TFAM1), B - subunit 1 mitochondrial cytochrome c oxidase (MTCO1). The data are presented as the mean of three measurements ± the standard error of the mean, n = 12 for each group

References

1. Allison J.L., Schust D.J. Recurrent first trimester pregnancy loss: revised definitions and novel causes. Curr. Opin. Endocrinol. Diabetes Obes. 2009; 16(6): 446-50.

2. Serova O.F., Tamazyan G.V., Sovaev N.I., Trifonova I.A., Eliseev E.N. Clinical significance of the morphofunctional state of the endometrium in the violation of reproductive function. Voprosyi ginekologii, akusherstva i perinatologii. 2010; 9(4): 43-8. (in Russian)

3. Makarov O.V., Khashukoeva A.Z., Svitich O.A., Markova E.A., Khlynova S.A. Estimation of cytokine profile during chemosensitized blood photomodification in patients with a history of recurrent miscarriage of viral genesis. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2014; (8): 19-26. (in Russian)

4. Porter T.F., Scott J.R. Evidence-based care of recurrent miscarriage. Best Pract. Res. Clin. Obstet. Gynaecol. 2005; 19(1): 85-101.

5. Krasnopolskiy V.I., Serova O.F., Titchenko L.I., Petruhin V.A., Tumanova V.A., Zarochentseva N.V., Kapustina M.V., Melnik T.N., Lipovenko L.N., Bakotina I.V., Marchenko S.Yu., Tamazyan G.V., Gridchik A.L. Conducting pregnancy in women with a history of miscarriage. A manual for doctors. Moscow; 2007. (in Russian)

6. Zaynulina M.S., Kornyushina E.A., Bikmullina D.R. Thrombophilia: the etiological factor or pathogenetic aspect of the complicated course of pregnancy? Zhurnal akusherstva i zhenskih bolezney. 2010; 59(1): 18-30. (in Russian)

7. Makarov O.V., Volkova E.V., Lysyuk E.Yu., Kopylova Yu.V., Dzhokhadze L.S. Role of angiogenic growth factors in the pathogenesis of preeclampsia and placental insufficiency. Akusherstvo i ginekologiya/Obstetrics and gynecology. 2014; (12): 64-70. (in Russian)

8. Sidelnikova V.M. Habitual loss of pregnancy. Moscow: Triada-X; 2005. (in Russian)

9. Sidorova I.S., Milovanov A.P., Nikitina N.A., Rzaeva A.A., Bardachova A.V. Features of placentation in preeclampsia and eclampsia. Rossiyskiy vestnik akushera-ginekologa. 2014; 14(3): 4-10. (in Russian)

10. Ong F.S., Lin J.C., Das K., Grosu D.S., Fan J.B. Translational utility of next-generation sequencing. Genomics. 2013; 102(3): 137-9.

11. Kan N.E., Sirotkina E.A. Tyutyunnik, V.L., Vysokikh M.Yu., Kurchakova T.A., Volodina M.A., Tarasova N.V., Pyataeva S.V. Specific features of antioxidant defense in the mother-placenta-fetus system in intrauterine infection. Akusherstvo i ginekologiya/Obstetrics and Gynecology. 2016; (1): 40-46. (in Russian) http://dx.doi.org/10.18565/aig.2016.1.40-46 (in Russian)

12. Malyishkina A.I., Mozhaeva A.I., Voronin D.N. Features of the reactions of innate immunity in women with the threat of termination of pregnancy in the early stages. Rossiyskiy immunologicheskiy zhurnal. 2010; 4: 407-8. (in Russian)

13. Raj Rai. Debate: Should immunotherapy be used? No. In: Carp H.J.A., ed. Recurrent pregnancy loss: сauses, controversies, and treatment. 2nd ed. CRС Press; 2014: 265.

14. Tannetta D.S., Hunt K., Jones C.I., Davidson N., Coxon C.H., Ferguson D. et al. Syncytiotrophoblast extracellular vesicles from pre-eclampsia placentas differentially affect platelet function. PLoS One. 2015; 10(11): e0142538.

15. Wenceslau C.F., McCarthy C.G., Szasz T., Spitler K., Goulopoulou S., Webb R.C.; Working Group on DAMPs in Cardiovascular Disease. Mitochondrial damage-associated molecular patterns and vascular function. Eur. Heart J. 2014; 35(18): 1172-7.

16. Kohli S., Ranjan S., Hoffmann J., Kashif M., Daniel E.A. Maternal extracellular vesicles and platelets promote preeclampsia via inflammasome activation in trophoblasts Blood. 2016; 128(17): 2153-64.

Received 03.11.2016

Accepted 11.11.2016

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 Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: vpa2002@mail.ru
Vysokikh Mikhail Yu., 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
Sukhikh Gennadiy Tikhonovich, Academician of RAS, MD, PhD, Professor, Director, Research Center of Obstetrics, Gynecology and Perinatology,
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. Tel.: +74954381800. E-mail: g_sukhikh@oparina4.ru

For citations: Bulatova Yu.S., Tetruashvili N.K.,
Vishnyakova P.A., Vysokikh M.Yu., Marei M.V., Pyataeva S.V., Sukhikh G.T. Mitochondrial proteins of peripheral plasma microvesicles as biomarkers of early pregnancy losses.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2017; (7): 46-51. (in Russian)
http://dx.doi.org/10.18565/aig.2017.7.46-51

Similar Articles

By continuing to use our site, you consent to the processing of cookies that ensure the proper functioning of the site.