Placental markers of miscarriage

Authors

  • A. A. Zhyvetska-Denysova State Institution “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine https://orcid.org/0000-0001-8418-5740
  • I. I. Vorobiova State Institution “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine https://orcid.org/0000-0002-6836-5845
  • N. Ya. Skrypchenko State Institution “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine https://orcid.org/0000-0003-2849-8499
  • S. M. Tolkach State Institution “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine https://orcid.org/0000-0003-0753-8869
  • S. M. Razdaibedin Bogomolets National Medical University, Kyiv, Ukraine, Ukraine
  • Yu. M. Bondarenko SI “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Аcademy of Мedical Sciences of Ukraine”, Kyiv, Ukraine

DOI:

https://doi.org/10.14739/2310-1237.2021.3.232302

Keywords:

pregnancy, miscarriage, chorion, placenta, VEGF, CD31, PECAM1, CD105, endoglin, TGFβ 1/3 receptor, TNF-alpha, CD45/T200/LCA, CD56, NCAM1

Abstract

Successful implantation involves a high degree of development of spiral arteries, combined with high proliferative activity, which ensures the formation of a healthy placenta, full uterine-placental circulation, and the birth of a healthy child. The placenta is the unique organ of the biological monitoring, the mirror of pregnancy. Identification of placental markers of miscarriage is a promising direction for preventing reproductive losses.

The aim of the work is to identify the markers of miscarriage and premature labor in the structures of the chorion and placenta.

Materials and methods. The main group included tissue samples of the 22 chorions and 64 placentas after termination of current pregnancy from women with a history of reproductive losses. The control group included tissue samples of the 20 chorions after artificial abortion and 20 placentas after physiological pregnancy and birth. The placenta was examined according to the protocol (form No. 013-1/0). The expressions of VEGF, CD31/PECAM1, CD105/Endoglin/TGFβ 1/3 Receptor, Bcl-2α Ab-1, TNF-α, CD45/T200/LCA, CD56/NCAM1 were studied in the structures of chorion and placenta by immunohistochemistry.

Results. Based on histological and immuno-histochemical study of chorion and placenta samples in women with reproductive history and termination of the current pregnancy, it was established that embryo-endometrial dysfunction is the cause of miscarriage in the first trimester, and inflammation is the precondition of preterm birth; markers of miscarriage and premature labor in the structures of the chorion and placenta have been identified.

Conclusions. The markers of miscarriage are pathomorphological changes in endometrium and chorion combined with high expression of TNF-α and NK-CD56, low expression of CD31/PECAM1, negative expression of VEGF to indicate a violation of cytotrophoblast invasions. The markers of inflammation and premature labor are structural and functional changes of placenta in combination with moderate expression of TNF-α in syncytium, high expression of NK-CD56 in villous stroma, high expression of CD45/T200/LCA in the decidual membrane.

Author Biographies

A. A. Zhyvetska-Denysova, State Institution “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Academy of Medical Sciences of Ukraine”, Kyiv

MD, PhD, Senior Researcher of the Department of Scientific Problems of Miscarriage

I. I. Vorobiova, State Institution “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Academy of Medical Sciences of Ukraine”, Kyiv

MD, PhD, DSc, Head of the Department of Scientific Problems of Miscarriage

N. Ya. Skrypchenko, State Institution “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Academy of Medical Sciences of Ukraine”, Kyiv

MD, PhD, DSc, Head of the Department of Introduction and Research of Modern Medical Technologies Effectiveness in Obstetrics and Perinatology

S. M. Tolkach, State Institution “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Academy of Medical Sciences of Ukraine”, Kyiv

MD, PhD, Leading Researcher of the Department of Scientific Problems of Miscarriage

S. M. Razdaibedin, Bogomolets National Medical University, Kyiv, Ukraine

MD, PhD, Associate Professor of the Department of Dermatology and Venereology with a Course of Cosmetology

Yu. M. Bondarenko, SI “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Аcademy of Мedical Sciences of Ukraine”, Kyiv

Junior Researcher, Laboratory of Pathomorphology

References

Tetruashvili, N. K. (2017). Privychnyy vykidysh [Habitual miscarriage]. Akusherstvo i ginekologíya: novosti, mneniya, obucheniye, (4), 70-87. [in Russian]. https://doi.org/10.24411/2303-9698-2017-00010

Chechuga, S. B., Nochvina, E. A., & Abdallah Sali. (2012). Patogeneticheskaya terapiya nevynashivaniya beremennosti u zhenshchin s gipergomotsisteinemiyey i gestagennoy nedostatochnost’yu [Pathogenetic therapy of miscarriage in women with hyperhomocysteinemia and progesterone deficiency]. Zdorovie zhenshiny, (5), 80-85. [in Ukrainian].

Zhivetskaya-Denisova, A. A., Vorobyova, I. I., Tkachenko, V. B., Podolskyi, V. V., & Tykha, V. G. (2019). Platsenta yak dzerkalo vahitnosti (Ohliad literatury) [Placenta - mirror of pregnancy (literature review)]. Zdorov’e zhenshchiny, (3), 101-106. [in Ukrainian].

Antipkin, Yu. G., Zadorozhnaya, T. D., & Parnitskaya, O. I. (Eds.). (2016). Patologiya placenty (sovremennye aspekty) [Pathology of placenta: modern aspects]. Кyiv. [in Russian].

Zhyvetska-Denysova A. A., Vorobiova I. I., Skrypchenko N. Ya., & Tkachenko V. B. (2020). Osoblyvosti tsytokinovoho profiliu v strukturakh khorionu ta platsenty pry peredchasnomu pereryvanni vahitnosti [Features of the cytokine profile in the structures of chorion and placenta in premature termination of pregnancy]. Pathologia, 17(2), 191-201. [in Ukrainian]. https://doi.org/10.14739/2310-1237.2020.2.212790

Redline, R. W. (2015). Classification of placental lesions. American Journal of Obstetrics & Gynecology, 213(4), 21-28. https://doi.org/10.1016/j.ajog.2015.05.056

Veropotvelyan, N. P., Veropotvelyan, P. N., Tsehmistrenko, I. S., Bondarenko, A. A., & Usenko, T. V. (2016). Morfologicheskaya klassifikatsiya povrezhdeniy platsenty [Morphological classification of lesions of the placenta]. Zdorov’e zhenshchiny, (8), 63-71. [in Russian]. https://doi.org/10.15574/hw.2016.114.63

Shegolev, A. I. (2016). Sovremennaya morfologicheskaya klassifikatsiya povrezhdenii platsenty [Current morphological classification of damages to the placenta]. Akusherstvo i ginekologiya, (4), 16-23. [in Russian]. http://doi.org/10.18565/aig.2016.4.16-23

Khong, T. Y., Mooney, E. E., Nikkels, P. G. J., Morgan, T. K., & Gordijn, S. J. (Eds.). (2019). Pathology of the Placenta: A Practical Guide. Switzerland: Springer Nature. https://doi.org/10.1007/978-3-319-97214-5

Ramazanova, E., Bapaeva, G., Akhmedianova, G., Hozhamuratova, А., Alisheva, А., & Shuganova, А. (2017). Immunologicheskiye aspekty nerazvivayushcheysya beremennosti v pervom trimestre gestatsii (obzornaya stat’ya) [Immunological aspects of missed abortion of the first trimester gestation]. Vestnik Kazakhskogo Natsional’nogo meditsinskogo universiteta, (4), 15-19. [in Russian].

Peretiatko, L. P., Fateeva, N. V., Kuznetsov, R. A., & Malyshkina A. I. (2017). Vaskulyarizatsiya vorsin khoriona v pervom trimestre beremennosti pri fiziologicheskom techenii i privychnom nevynashivanii na fone khronicheskogo endometrita [Vascularization of chorion villi in the first trimester of gestation with physiological course and in recurrent miscarriage with underlying chronic endometritis]. I. P. Pavlov Russian Medical Biological Herald, 25(4), 612-620. [in Russian]. https://doi.org/10.23888/PAVLOVJ20174612-620

Cöl-Madendag, I., Madendag, Y., Altinkaya, S. Ö., Bayramoglu, H., & Danisman, N. (2014). The role of VEGF and its receptors in the etiology of early pregnancy loss. Gynecological endocrinology, 30(2), 153-156. https://doi.org/ 10.3109/09513590.2013.864272

Okada, H., Tsuzuki, T., Shindoh, H., Nishigaki, A., Yasuda, K., & Kanzaki, H. (2014). Regulation of decidualization and angiogenesis in the human endometrium: mini review. The journal of obstetrics and gynecology research, 40(5), 1180-1187. https://doi.org/10.1111/jog.12392

Volkova, E. V., & Kopylova, Yu. V. (2013). Rol’ sosudistykh faktorov rosta v patogeneze platsentarnoy nedostatochnosti [The role of vascular growth factors in the pathogenesis of placental insufficiency]. Akusherstvo, ginekologiya i reproduktsiya, 7(2), 29-33. [in Russian].

Sementsova, N. A., Ponomareva, Ju. N., Barsanova, T. G., & Zayratyants, O. V. (2012). Narushenie protsessov angiogeneza, apoptoza i proliferatsii v tkanyakh plodnogo yaitsa i endometrii pri nerazvivayushcheisya beremennosti v I trimester [Disorders of angiogenesis, apoptosis and proliferation in the tissue of the gestational sac and endometrium in non-developing pregnancy]. Klinicheskaya i eksperimentalnaya morfologiya, (3), 11-16. [in Russian].

Kajdaniuk, D., Marek, B., Borgiel-Marek, H., & Kos-Kudła B. (2013). Transforming growth factor β1 (TGFβ1) in physiology and pathology. Endokrynologia Polska, 64(5), 384-96. https://doi.org/10.5603/EP.2013.0022

Batrak, N. V., Malyshkina, A. I., & Kroshkina, N. V. (2014). Immunologicheskie aspekty privychnogo nevynashivaniya beremennosti [Immunological aspects of habitual miscarriage]. Akusherstvo i ginekologiya, (12), 10-14. [in Russian].

Alijotas-Reig, J., Llurba, E., & Gris, J. M. (2014). Potentiating maternal immune tolerance in pregnancy: a new challenging role for regulatory T cells. Placenta, 35(4), 241-248. https://doi.org/10.1016/j.placenta.2014.02.004

Dobrokhotova, Yu. E., Gankovskaya, L. V., Bakhareva, I. V., Svitich, O. A., Malushenko, S. V., & Magomedova, A. M. (2016). Rol’ immunnykh mekhanizmov v patogeneze nevynashivaniya beremennosti [Role of immune mechanisms in the pathogenesis of miscarriage]. Akusherstvo i hinekolohiia, (7), 5-10. [in Russian]. http://doi.org/10.18565/aig.2016.7.5-10

Vacca, P., Vitale, Ch., Munari, E., Cassatella, M. A., Mingari, M. C., & Moretta L. (2018). Human Innate Lymphoid Cells: Their Functional and Cellular Interactions in Decidua. Frontiers in Immunology, (9), 1897. https://doi.org/10.3389/fimmu.2018.01897

Matson, B. C., & Caron, K. M. (2014). Uterine natural killer cells as modulators of the maternal-fetal vasculature. The International journal of developmental biology, 58(2-4), 199-204. https://doi.org/10.1387/ijdb.140032kc

Jabrane-Ferrat, N., & Siewiera, J. (2014). The up side of decidual natural killer cells: new developments in immunology of pregnancy. Immunology, 141(4), 490-497. https://doi.org/10.1111/imm.12218

Vorobyeva, I. I., Skripchenko, N. Y., Tkachenko, V. B., Tolkach, S. M., & Hrazdaybedin, S. M. (2020). Osoblyvosti rozvytku zapal’nykh reaktsiy u platsenti pry polohakh na riznykh terminakh hestatsiyi [Peculiarities of the inflammatory reactions development in placenta at delivery in different gestational terms]. Reproduktyvna endokrynolohiya, (2), 44-48. [in Ukrainian].

Chernobai, L. V., Tyshchenko, A. N., Lazurenko, V. V., Muryzina, I. Yu., & Yurkova, O. V. (2016). Rol’ narusheniya tsitokinovogo profilya v snizhenii fertil’nosti [The role of cytokine profile disruption in fertility reduction]. Mizhnarodnyi medychnyi zhurnal, (2), 38-43. [in Russian].

Yuan, J., Li, J., Huang, S. Y., & Sun, X. (2015). Characterization of the subsets of human NK T-like cells and the expression of Th1/Th2 cytokines in patients with unexplained recurrent spontaneous abortion. Journal of reproductive immunology, (110), 81-88. https://doi.org/10.1016/j.jri.2015.05.001

Azizieh, F. Y., & Raghupathy R. G. (2015). Tumor necrosis factor-α and pregnancy complications: a prospective study. Medical principles and practice, 24(2), 165-170. https://doi.org/10.1159/000369363

Polushkina, E. S., & Shmakov, R. G. (2020). Rol’ didrogesterona v privychnom nevynashivanii beremennosti [The role of dydrogesterone in habitual miscarriage]. Meditsinskiy sovet, (3), 74-77. [in Russian]. https://doi.org/10.21518/2079-701X-2020-3-74-77

Avtandilov, G. G. (1990). Medicinskaya morfometriya [Medical morphometry]. Moscow: Meditsina. [in Russian].

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Published

2021-12-01

How to Cite

1.
Zhyvetska-Denysova AA, Vorobiova II, Skrypchenko NY, Tolkach SM, Razdaibedin SM, Bondarenko YM. Placental markers of miscarriage. Pathologia [Internet]. 2021Dec.1 [cited 2024Nov.9];18(3):328-39. Available from: http://pat.zsmu.edu.ua/article/view/232302

Issue

Vol. 18 No. 3 (2021): Pathologia

Section

Original research

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