Immunohistochemical and Ultrastructural Features of Multinucleated Giant Trophoblast Cells in Abnormally Invasive Placenta
https://doi.org/10.18499/2225-7357-2026-15-1-38-49
Abstract
The aim of the study was to assess the morphological, ultrastructural, and immunohistochemical features of multinucleated giant trophoblast cells (MGTCs) within the myometrium of women (at 34– 38 weeks of gestation) presenting with abnormally invasive placenta.
Material and methods. The study included 31 pregnant women aged 27–43 years, of whom 19 women (at 34–38 weeks of gestation) had pathological placental attachment, with identified placenta accreta (n=7) and placenta increta (n=12) into the uterine wall. The comparison group consisted of women (n=12) without pathological placental attachment. Myometrial fragments were fixed in 10% formalin solution, embedded in paraffin, and stained with hematoxylin and eosin. Immunohistochemical examination was performed on paraffin sections of the placenta using primary antibodies to cytokeratin 8, CD68, TF (tissue factor), CD163, CD206, CD14, CD16, IGFBP-1, placental lactogen (PL), and bhCG; ultrastructural features of MGTCs were also studied.
Results. The epithelial phenotype of MGTCs was confirmed by the detection of cytokeratin 8, weak expression of placental lactogen, b-hCG, tissue factor, and the absence of expression of both macrophage lineage markers (CD68, CD206, CD14, CD16, CD163) and the decidual cell marker (IGFBP-1). In samples from the comparison group, MGTCs were sparse. The identified ultrastructural features MGTCs such as a significant number of granular endoplasmic reticulum cisternae, the presence of numerous mitochondria, and Golgi complex structures — indicate their high synthetic and secretory activity. At the same time, the presence of multiple microvilli on their surface suggests the capacity for further invasion, which may be particularly important in placenta increta.
Conclusion. Thus, the epithelial origin of MGTCs was confirmed, and their high synthetic activity, as well as their ability to invade and migrate into the uterine wall, was demonstrated.
About the Authors
N. V. NizyaevaRussian Federation
Natal'ya V. Nizyaeva – Doct. Sci. (Med.), Head of Reproductive Pathology Laboratory, Avtsyn Research Institute of Human Morphology
per. Abrikosovskii, 2, Moscow, 119991
T. V. Sukhacheva
Russian Federation
Tat'yana V. Sukhacheva – Cand. Sci (Biol.), Senior Researcher of Reproductive Pathology Laboratory, Avtsyn Research Institute of Human Morphology
Moscow
E. R. Milyutina
Russian Federation
Ekaterina R. Milyutina – obstetrician-gynecologist of the maternity ward
Vidnoye
N. A. Gabitova
Russian Federation
Nataliya A. Gabitova – Dr. Sci (Med.), Prof., Department of Pregnancy Pathology
Vidnoye
T. N. Belousova
Russian Federation
Tamara N. Belousova – Cand. Sci (Med.), Head
Vidnoye
T. V. Fokina
Russian Federation
Tat'yana V. Fokina – Cand. Sci (Med.), Senior Researcher of Reproductive Pathology Laboratory, Avtsyn Research Institute of Human Morphology
Moscow
T. D. Patsaev
Russian Federation
Timofei D. Patsaev – Junior Researcher at the Resource Center for Probe and Electron Microscopy
Moscow
M. V. Mnikhovich
Russian Federation
Maksim V. Mnikhovich – Cand. Sci. (Med.), Associate Professor, leading researcher of Central pathoanatomical laboratory of A.P. Avtsyn Research Institute of Human Morphology; Head of the Department of Normal Human Anatomy of B.V. Petrovsky Medical University
Moscow
L. M. Mikhaleva
Russian Federation
Lyudmila M. Mikhaleva – Doct. Sci. (Med.), Head of Clinical Morphology Laboratory, Avtsyn Research Institute of Human Morphology
Moscow
M. N. Babaeva
Russian Federation
Mariya N. Babaeva – Junior Researcher of Reproductive Pathology Laboratory, Avtsyn Research Institute of Human Morphology
Moscow
References
1. Kulikov IA, Nizyaeva NV, Sukhacheva TV, Serov RA, Tikhonova NB, Fokina TV, et al. Sravnitelnaya morfologicheskaya kharakteristika matochno-platsentarnoi oblasti pri anomalnom prikreplenii platsenty [Comparative morphological characteristics of the uteroplacental area in abnormal placentation]. Acta Biomedica Scientifica. 2023;8(4):68-79. (In Russ.). doi:10.29413/ABS.2023-8.4.8
2. Kulikov IA, Artemyeva KA, Aleksankin AP, Milyutina ER, Stepanova II, Nizyaeva NV, et al. Morfofunktsional'nye, molekulyarnye i immunologicheskie izmeneniya v platsente i perifericheskoi krovi pri patologicheskom prikreplenii platsenty [Placental and peripheral blood changes in functional morphology and immunology in patients with placenta accreta spectrum]. Klinicheskaya i eksperimental'naya morfologiya. 2024; 13(3): 42-52. (In Russ.). doi: 10.31088/CEM2024.13.3.42-52.
3. Milovanov AP, Rasstrigina IM, Fokina TV. Morfometricheskaya otsenka plotnosti raspredeleniya i diametra kletok vnevorsinchatogo trofoblasta v techenie uslovno-neoslozhnennoi beremennosti [Morphometric evaluation of the frequency distribution and diameter of extravillous trophoblast cells in apparently uncomplicated pregnancy]. Arkhiv patologii. 2013;75(3):18-21. (In Russ.).
4. Milovanov AP. Tsitotrofoblasticheskaya invaziya — vazhneishii mekhanizm platsentatsii i progressii beremennosti. [Cytotrophoblastic invasion is the most important mechanism of placentation and pregnancy progression]. Archive of Pathology = Arkhiv patologii. 2019;81(4):5-10. (In Russ.). doi: 10.17116/patol2019810415.
5. Nizyaeva NV, Kulikov IA, Belousova TN, Artemieva KA, Milovanov AP, Tikhonova NB, et al. Placenta percreta: platsentarnaya vorsinchataya invaziya ili variant spaechnoi bolezni? [Placenta percreta: placental villous invasion or a form of adhesive disease?] Klinicheskaya i eksperimental'naya morfologiya. 2024;13(4):76-85. (In Russ.). doi: 10.31088/CEM2024.13.4.76-85.
6. Stepanova II, Artemyeva KA, Stepanov AA, Bogdanova IM, Ponomarenko EA, Boltovskaya MN. Primenenie kletochnogo immunofermentnogo analiza dlya skrininga gibridom i polucheniya perspektivnykh produtsentov monoklonal'nykh antitel [Application of In-Cell ELISA assay for hybridoma screening and selection of promising producers of monoclonal antibodies]. Uchenye zapiski Kazanskogo universiteta. Seriya Estestvennye nauki. 2022;164(4):535–550. (In Russ.). doi: 10.26907/2542-064X.2022.4.535-550.
7. al-Lamki RS, Skepper JN, Burton GJ. Are human placental bed giant cells merely aggregates of small mononuclear trophoblast cells? An ultrastructural and immunocytochemical study. Hum Reprod. 1999 Feb;14(2):496-504. doi: 10.1093/humrep/14.2.496.
8. Dachet F, Brown JB, Valyi-Nagy T, Narayan KD, Serafini A, Boley N, et al. Selective timedependent changes in activity and cell-specific gene expression in human postmortem brain. Sci Rep. 2021 Mar 23;11(1):6078. doi: 10.1038/s41598-021-85801-6.
9. D'Souza AW, Wagner GP. Malignant cancer and invasive placentation: A case for positive pleiotropy between endometrial and malignancy phenotypes. Evol Med Public Health. 2014 Oct 15;2014(1):136-45. doi: 10.1093/emph/eou022.
10. Gong Y, Fan Z, Luo G, Yang C, Huang Q, Fan K, et al. The role of necroptosis in cancer biology and therapy. Mol Cancer. 2019 May 23;18(1):100. doi: 10.1186/s12943-019-1029-8.
11. Hayakawa K, Terada K, Takahashi T, Oana H, Washizu M, Tanaka S. Nucleosomes of polyploid trophoblast giant cells mostly consist of histone variants and form a loose chromatin structure. Sci Rep. 2018 Apr 11;8(1):5811. doi: 10.1038/s41598-018-23832-2.
12. Humphries F., Wang S., Wang B., et al. RIP kinases: key decision makers in cell death and innate immunity. Cell Death & Differentiation. 2015 Feb;22(2): 225–236. DOI:10.1038/cdd.2014.126.
13. Jauniaux E, Ayres-de-Campos D, Langhoff-Roos J, Fox KA, Collins S; FIGO Placenta Accreta Diagnosis and Management Expert Consensus Panel. FIGO classification for the clinical diagnosis of placenta accreta spectrum disorders. Int J Gynaecol Obstet. 2019 Jul;146(1):20-24. doi: 10.1002/ijgo.12761.
14. Jauniaux E, Bunce C, Grønbeck L, Langhoff-Roos J. Prevalence and main outcomes of placenta accreta spectrum: a systematic review and metaanalysis. Am J Obstet Gynecol. 2019 Sep;221(3):208-218. doi: 10.1016/j.ajog.2019.01.233.
15. Jones CJP, Aplin JD. A re-examination of the origins of placental bed giant cells. Placenta. 2021 Oct;114:39-41. doi: 10.1016/j.placenta.2021.08.053.
16. Li X, Li ZH, Wang YX, Liu TH. A comprehensive review of human trophoblast fusion models: recent developments and challenges. Cell Death Discov. 2023 Oct 10;9(1):372. doi: 10.1038/s41420-023-01670-0.
17. Morey R, Farah O, Kallol S, Requena DF, Meads M, Moretto-Zita M, et al. Transcriptomic Drivers of Differentiation, Maturation, and Polyploidy in Human Extravillous Trophoblast. Front Cell Dev Biol. 2021 Sep 3;9:702046. doi: 10.3389/fcell.2021.702046. Erratum in: Front Cell Dev Biol. 2023 Mar 28;11:1189745. doi: 10.3389/fcell.2023.1189745.
18. Park SY, Hong HJ, Lee HJ. Fabrication of Cell Spheroids for 3D Cell Culture and Biomedical Applications. BioChip J 17, 24–43 (2023). doi: 10.1007/s13206-022-00086-9.
19. Renaud SJ, Jeyarajah MJ. How trophoblasts fuse: an in-depth look into placental syncytiotrophoblast formation. Cell Mol Life Sci. 2022 Jul 20;79(8):433. doi: 10.1007/s00018-022-04475-z
20. Stanek J, Biesiada J. Sensitivity and specificity of finding of multinucleate trophoblastic giant cells in decidua in placentas from high-risk pregnancies. Hum Pathol. 2012 Feb;43(2):261-8. doi: 10.1016/j.humpath.2011.03.012
21. van Beekhuizen HJ, Joosten I, de Groot AN, Lotgering FK, van der Laak J, Bulten J. The number of multinucleated trophoblastic giant cells in the basal decidua is decreased in retained placenta. J Clin Pathol. 2009 Sep;62(9):794-7. doi: 10.1136/jcp.2009.065953
Review
For citations:
Nizyaeva N.V., Sukhacheva T.V., Milyutina E.R., Gabitova N.A., Belousova T.N., Fokina T.V., Patsaev T.D., Mnikhovich M.V., Mikhaleva L.M., Babaeva M.N. Immunohistochemical and Ultrastructural Features of Multinucleated Giant Trophoblast Cells in Abnormally Invasive Placenta. Journal of Anatomy and Histopathology. 2026;15(1):38-49. (In Russ.) https://doi.org/10.18499/2225-7357-2026-15-1-38-49
JATS XML
























