Genetic determinants of adenomyosis

Malysheva O.V., Yarmolinskaya M.I.

1) D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproduction, Saint Petersburg, Russia; 2) I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia, Saint Petersburg, Russia
Adenomyosis is defined as the presence of endometrial-like tissue within the myometrium. It is a multifactorial disease with possible genetic predisposition. This article presents the results of the studies carried out within the framework of three approaches: association analysis, gene expression study and somatic mutation study. According to the classical concepts, the genetic predisposition to multifactorial diseases (including adenomyosis) depends on the presence of a certain set of polymorphic gene variants in a person. Such investigations are very few in adenomyosis; most of the studies are devoted to the analysis of gene variants whose products are involved in the synthesis and metabolism of estrogens, neoangiogenesis and remodeling of the extracellular matrix. Moreover, epigenetic mechanisms of adenomyosis can cause long-term changes in the expression of individual genes or entire blocks of genes due to DNA methylation, changes in the structure of chromatin, and non-coding RNAs. The article highlights a new area of research devoted to the study of the role of somatic mutations in adenomyosis. In comparison with other tissues, the endometrial glands of healthy women carry a particularly large number of somatic mutations, while stromal cells mostly remain intact. Somatic mutations in epithelial cells are also found in the ectopic endometrium of patients with adenomyosis and extragenital endometriosis. The spectra of somatic mutations detected in the ectopic endometrium in extragenital endometriosis and adenomyosis have their own characteristics and they are different in these two diseases.
Conclusion: The above genetic aspects of pathogenic mechanisms of adenomyosis indicate that this disease has a polyetiological origin. The presence of unfavorable alleles that impair the functioning of gene networks associated with the pathogenesis of the disease, long-term changes in gene expression followed by disorders in tissue homeostasis in target organs, and appearance of somatic mutations in the cells of the glands of the ectopic and eutopic endometrium are the factors that together can lead to the development of this pathology.

Authors’ contributions: Malysheva O.V., Yarmolinskaya M.I. – developing the concept and design of the study, collecting and processing the material; Malysheva O.V. – writing the text; Yarmolinskaya M.I. – editing the article.
Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: The study was conducted within the framework of the Basic Scientific Research project, “Strategy of preserving the health of women with gynecological and endocrine diseases in different age periods: pathogenetic rationale for drug rehabilitation and development of new directions of organ‑preserving surgical interventions”, No. 122041500063‑2.
For citation: Malysheva O.V., Yarmolinskaya M.I. Genetic determinants of adenomyosis. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2023; (4): 20-27 (in Russian)


genetic predisposition
single nucleotide polymorphism
gene expression
somatic mutation
DNA methylation


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Received 01.03.2023

Accepted 29.03.2023

About the Authors

Olga V. Malysheva, Senior Researcher, Laboratory of Genomics, D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology, +7(812)328-98-09,,, 199034, Russia, St. Petersburg, Mendeleyevskaya liniya, 3.
Maria I. Yarmolinskaya, Professor of RAS, Dr. Med. Sci., Head of the Department of Gynecology and Endocrinology, D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology, 199034, Russia, St. Petersburg, Mendeleyevskaya liniya, 3; Professor, Department of Obstetrics and Gynecology, I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia, 191015, Russia, St. Petersburg, Kirochnaya str., 41,, Corresponding author: Olga V. Malysheva,

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