Immunophenotypic endometrium profile in experimental hyperplasia

Aim. To study the topography and expression of cell cycle markers, as well as those of inflammation and immune response, by the method of immunohistochemistry using an experimental model of endometrial hyperplasia.

Materials and methods. Endometrial hyperplasia was modeled in laboratory rats by ovariectomy and transdermal administration of estrogen to form hyperestrogenism. Morphological changes were verified by a histological method. The immunophenotypic profile was assessed by immunohistochemistry. The obtained digital values were processed by mathematical and statistical methods.

Results. The modelled endometrial hyperplasia indicated an increase in the glandular component, a decrease in the expression of estrogen receptors in the uterine horns, an increase in the mitotic activity of epithelial cells in the uterine body, an activation of cell apoptosis in all its departments, as well as a decrease in the expression of plasmocyte markers (CD138) in the stroma of all parts of the uterus and T-lymphocytes (CD8) in the stroma the body of the uterus.

Conclusion. Structural changes in endometrial hyperplasia in the setting of hyperestrogenism are caused by cell cycle dysregulation. At the same time, intracellular autoregulation systems are more effective in the uterine horns, with no changes being observed in the expression of estrogen receptors in the uterine body and the mitotic activity of cells being increased. Given the deficiency of immunocompetent T cells, the risk of tissue and cellular transformations increases in this area.

1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. doi: 10.3322/caac.21492

2. Volotskaya NI, Sulima AN, Rumyantseva ZS. Menopause: modern standards for diagnosis and correction of disorders. Vrach = The Doctor. 2021;32(3):66–72 (In Russ.). doi: 10.29296/25877305-2021-03-12

3. Karapetyan OV, Fomochkina II, Zyablitskaya Y, Kubyshkin VA, Kovalenko EP, Korobova PG, Makalish TP, Kubyshkin AV. The state of local markers of inflammation and apoptosis in endometry in hyperplasia of various degrees of severity. Meditsinskii Vestnik Severnogo Kavkaza = Medical News of the North Caucasus, 2020;15(3):342–7 (In Russ.). doi: 10.1158/2159-8290.CD-21-1059

4. Kubyshkin AV, Aliev LL, Fomochkina II, Kovalenko YP, Litvinova SV, Filonenko TG, Lomakin NV, Kubyshkin VA, Karapetian OV. Endometrial hyperplasia-related inflammation: its role in the development and progression of endometrial hyperplasia. Inflamm Res. 2016;65(10):785–94. doi: 10.1007/s00011-016-0960-z

5. Faloppa CC, Baiocchi G, Cunha IW, Fregnani JH, Osorio CA, Fukazawa EM, Kumagai LY, Badiglian-Filho L, Pinto GL, Soares FA. NF-κB and COX-2 expression in nonmalignant endometrial lesions and cancer. Am J Clin Pathol. 2014;141(2):196–203. doi: 10.1309/AJCPV7U7PGHOWEQG

6. Morsy MA, Abdelraheem WM, El-Hussieny M, Refaie MMM. Protective Effects of Irbesartan, an Angiotensin Receptor Blocker with PPARγ Agonistic Activity, against Estradiol BenzoateInduced Endometrial Hyperplasia and Atypia in Female Rats via Modulation of TNFα/Survivin Pathway. Pharmaceuticals (Basel). 2021;14(7):649. doi: 10.3390/ph14070649

7. Gellersen B, Brosens JJ. Cyclic decidualization of the human endometrium in reproductive health and failure. Endocr Rev. 2014;35(6):851–905. doi: 10.1210/er.2014-1045

8. Santamaria X, Mas A, Cervelló I, Taylor H, Simon C. Uterine stem cells: from basic research to advanced cell therapies. Hum Reprod Update. 2018;24(6):673–93. doi: 10.1093/humupd/dmy028

9. Terzic M, Aimagambetova G, Kunz J, Bapayeva G, Aitbayeva B, Terzic S, Laganà AS. Molecular Basis of Endometriosis and Endometrial Cancer: Current Knowledge and Future Perspectives. Int J Mol Sci. 2021;22(17):9274. doi: 10.3390/ijms22179274

10. Gibson DA, Saunders PT. Estrogen dependent signaling in reproductive tissues – a role for estrogen receptors and estrogen related receptors. Mol Cell Endocrinol. 2012;348(2):361–72. doi: 10.1016/j.mce.2011.09.026

11. Singh S, Pavuluri S, Jyothi Lakshmi B, Biswa BB, Venkatachalam B, Tripura C, Kumar S. Molecular characterization of Wdr13 knockout female mice uteri: a model for human endometrial hyperplasia. Sci Rep. 2020;10(1):14621. doi: 10.1038/s41598-020-70773-w

12. Gabidullina RI, Smirnova GA, Nukhbala FR, Valeeva EV, Orlova YuI, Shakirov AA. Hyperplastic endometrial processes: Modern tactics of patient management. Consilium Medicum. 2019;21(6): 53–8 (In Russ.). doi: 10.26442/20795696.2019.6.190472

13. Refaie MMM, El-Hussieny M. The role of interleukin-1b and its antagonist (diacerein) in estradiol benzoate-induced endometrial hyperplasia and atypia in female rats. Fundam Clin Pharmacol. 2017;31(4):438–46. doi: 10.1111/fcp.12285

14. Royal College of Obstetrician and ginecologists. Management of Endometrial Hyperplasia. GreenTop Guideline No.67. RCOG/ BSGE Joint Guideline – February 2016.

15. Hanahan D. Hallmarks of Cancer: New Dimensions. Cancer Discov. 2022;12(1):31–46. doi: 1158/2159-8290.CD-21-1059