Current views on the role of genetic disorders in the etiology and pathogenesis of endometriosis
The paper analyzes the data available in the literature on the results of investigating the sequences and relationships of genetic disorders in endometriosis. Hereditary predisposition to this disease is characteristic for women with clinical manifestations of endometriosis. This category of patients is noted to have epigenetic disorders in the progenitor cells and stem cells of the coelomic epithelium, endometrium, endometrial vasculature, and in other tissues of the reproductive system. Critical disorders of genome-wide DNA methylation and changes in the signaling pathways of gene expression regulation are shown to be characteristic for endometrioid stromal cells. Most of these disorders develop in the stromal cells that have the properties of stem cells and partially the characteristics of ovarian cell granules and immune cells, such as the production of estradiol, prostaglandin, and cytokines. These cells originating from the ectopic endometrium show the abnormal expression of a number of transcription factors that regulate key genes necessary for progesterone-regulated differentiation of normal endometrial stromal cells. It has been shown that the endometrial cells exhibit mutations, including driver mutations in ovarian cancer. Intense paracrine inflammatory signals, together with estrogens from epigenomically improperly programmed endometrioid cells, can lead to increased epithelial mutagenesis and activation of carcinogenesis.Kalimatova D.M., Dobrokhotova Yu.E.
Conclusion. It is necessary to further study the genetic aspects of endometriosis in order to deepen our understanding of the pathogenesis of the disease and to develop promising treatment methods.
Keywords
endometriosis
genetic polymorphism
endometrioid cells
heredity
candidate genes
somatic mutations
epigenome
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Received 02.07.2020
Accepted 05.03.2021
About the Authors
Donna M. Kalimatova, Ph.D., Associate Professor of the Department of Obstetrics and Gynecology of the Faculty of Medicine, N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia. Tel.: +7(926)922-77-07. E-mail: 9227707@gmail.com. ORCID: 0000-0002-2487-9086.117997, Russia, Moscow, Ostrovitianov str., 1/9.
Yulia E. Dobrokhotova, Dr. Med. Sci., professor, Head of the Department of Obstetrics and Gynecology of Medical Faculty, N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia. Tel.: +7(495)722-63-99. E-mail: pr.dobrohotova@mail.ru. 117997, Russia, Moscow, Ostrovitianov str., 1/9.
For citation: Kalimatova D.M., Dobrokhotova Yu.E. Current views on the role of genetic disorders in the etiology and pathogenesis of endometriosis.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2021; 3: 44-49 (in Russian)
https://dx.doi.org/10.18565/aig.2021.3.44-49