Expression of SMAD-dependent pathway components in the pathogenesis of hyperplastic processes of the endometrium in benign uterine diseases

Sarkisyan R.M., Gavrilova T.Yu., Asaturova A.V., Adamyan L.V.

1) Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, Moscow, Russia; 2) Russian University of Medicine, Ministry of Health of Russia, Moscow, Russia

Hyperplastic processes of the endometrium, including endometrial polyps and hyperplasia, are among the most common disorders of the female reproductive system. Modern studies on the pathogenesis of hyperplastic changes have focused on the molecular mechanisms that regulate cell proliferation and apoptosis. Among the key signaling pathways, the transforming growth factor (TGF-β) pathway plays a crucial role in regulating cell growth, differentiation, and apoptosis through both SMAD-dependent and SMAD-independent cascades.
Objective: To clarify the pathogenetic aspects of hyperplastic processes of the endometrium in conjunction with benign lesions of the uterine body (leiomyoma of the uterine body and adenomyosis) by studying the expression of components of the SMAD-dependent TGF-β signaling pathway.
Materials and methods: A comprehensive examination was conducted on 90 patients of reproductive age with various conditions: endometrial hyperplasia (group 1, n=15), endometrial polyps (group 2, n=15), endometrial polyps combined with uterine leiomyoma (group 3, n=15), endometrial polyps combined with adenomyosis (group 4, n=15), endometrial hyperplasia combined with uterine leiomyoma (group 5, n=15), and endometrial hyperplasia combined with adenomyosis (group 6, n=15). Clinical, laboratory, and instrumental data, along with the morphological and immunohistochemical characteristics of the endometrium before and after surgical treatment, were assessed.
Results: The expression of TGF-β signaling pathway components was found to be significantly increased in hyperplastic processes of the endometrium, particularly in cases of adenomyosis and uterine leiomyoma. A correlation was established between the expression levels of these pathway components and clinical and morphological characteristics, underscoring the importance of TGF-β in the pathogenesis of hyperplastic processes.
Conclusion: This study demonstrated that the TGF-β signaling pathway, especially its SMAD-dependent cascade, plays a vital role in the pathogenesis of endometrial hyperplastic processes. These findings highlight the potential of TGF-β signaling pathway components as diagnostic markers and emphasize the need for further research to develop effective targeted approaches for the treatment and prevention of the recurrence of endometrial hyperplastic processes.

Authors' contributions: Adamyan L.V., Asaturova A.V., Sarkisyan R.M. – conception and design of the study; Sarkisyan R.M., Gavrilova T.Yu., Asaturova A.V. – data acquisition and processing; Sarkisyan R.M., Asaturova A.V. – statistical analysis; Sarkisyan R.M., Asaturova A.V., Gavrilova T.Yu. – drafting of the manuscript; Adamyan L.V. – editing of the manuscript.
Conflicts of interest: The authors have no conflicts of interest to declare.
Funding: There was no finding for this study.
Ethical Approval: The study was reviewed and approved by the Research Ethics Committee of the V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia.
Patient Consent for Publication: All patients provided informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available upon request from the corresponding author after approval from the principal investigator.
For citation: Sarkisyan R.M., Gavrilova T.Yu., Asaturova A.V., Adamyan L.V. Expression of SMAD-dependent pathway components in the pathogenesis of hyperplastic processes of the endometrium in benign uterine diseases.
 Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (3): 102-112 (in Russian)
https://dx.doi.org/10.18565/aig.2025.14

Keywords

endometrial hyperplasia
endometrial polyp
uterine leiomyoma
adenomyosis
immunohistochemical study
reproductive age
components of the transforming growth factor beta signaling pathway
TGF-β

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Received 27.01.2025

Accepted 26.02.2025

About the Authors

Rita M. Sarkisyan, PhD student, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, ritamisakovna@mail.ru, https://orcid.org/0000-0002-4097-5537
Tatyana Yu. Gavrilova, Dr. Med. SCi., obstetrician-gynecologist at the Gynecological Department, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, t_gavrilova@oparina4.ru, https://orcid.org/0000-0001-7424-4292
Alexandra V. Asaturova, Dr. Med. Sci., Head of the 1st Pathological Anatomical Department, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, a.asaturova@gmail.com, https://orcid.org/0000-0001-8739-5209
Leila V. Adamyan, Academician of the Russian Academy of Sciences, Dr. Med. Sci., Professor, Deputy Director for Research, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4; Chief Specialist in Gynecology
of the Ministry of Health of Russia; Head of the Department of Reproductive Medicine and Surgery of the Faculty of Postgraduate Education, Russian University of Medicine, Ministry of Health of Russia, adamyanleila@gmail.com, https://orcid.org/0000-0002-3253-4512
Corresponding author: Rita M. Sarkisyan, ritamisakovna@mail.ru

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