Molecular and cellular landscape of endometriosis

Endometriosis is a prevalent benign gynecological disease in women of reproductive age. It is estimated to affect globally around 190 million people, or approximately every tenth woman. Symptomatically endometriosis usually manifests with chronic pelvic pain, impaired fertility and reduced quality of life. These nonspecific symptoms or asymptomatic course of disease make it difficult for women to suspect the presence of disease. Thereby, the diagnosis is often delayed on average for seven to nine years. In many cases, endometriosis is identified during medical examination and surgical intervention due to other pathology, or investigation of possible reasons for infertility. However, even after confirmation of endometriosis diagnosis women cannot be fully cured and their treatment is limited to the management of symptoms or surgical removal of endometriotic lesions (ectopic endometrium, EcE).

Endometriotic lesions are presented as extrauterine ectopic growth of endometrial-like tissues. They are mostly found in the peritoneum but can also form ovarian endometrioid cysts or spread locally or distally to other organs and tissues, affecting their function. The origin of this multifaceted disease remains unclear, and the theory of retrograde menstruation is the most widely accepted. According to this theory, fragments of shed endometrial tissues spread outside the uterus and implant on surrounding tissues and organs, adapting to the unfavorable microenvironment. Endometriotic lesions exhibit a molecular signature distinct from eutopic endometrium (EuE), which allows their survival and growth in ectopic sites. Research on the pathogenesis of endometriosis unraveled a key role of hormone imbalance and hypoxia on the regulation of processes, like cell proliferation, migration, metabolism and angiogenesis.

With the development of advanced powerful techniques, such as high-throughput transcriptomics, proteomics and metabolomics, we can perform a comprehensive analysis of tissues. Moreover, the identified molecular signatures can be linked to the single cell populations. By utilizing these techniques to study endometriosis pathogenesis, we can explore RNA, protein and metabolite profiles of single cell populations within endometriotic lesions. This knowledge will facilitate further understanding of disease pathobiology with potential applications in diagnostics and treatment of endometriosis.

LIST OF ORIGINAL PUBLICATIONS

I. Sarsenova, M.*, Lawarde, A.*, Pathare, A. D. S., Saare, M., Modhukur, V., Soplepmann, P., Terasmaa, A., Käämbre, T., Gemzell-Danielsson, K., Lalitkumar, P. G. L., Salumets, A., & Peters, M. (2024). Endometriotic lesions exhibit distinct metabolic signature compared to paired eutopic endometrium at the single-cell level. Communications Biology. 7(1), 1026. https://doi.org/10.1038/s42003-024-06713-5

II. Sarsenova, M., Boggavarapu NR., Kask K., Modhukur V., Samuel K., Karro H., Gemzell-Danielsson K., Lalitkumar PGL., Salumets A., Peters M., Lavogina D. (2024). Hypoxic conditions affect transcriptome of endometrial stromal cells in endometriosis and promote TGFBI axis. Frontiers in Endocrinology. 15. https://doi.org/10.3389/fendo.2024.1465393

III. Sarsenova, M., Stepanjuk, A., Saare, M., Kasvandik, S., Soplepmann, P., Mikeltadze, I., Götte, M., Salumets, A., & Peters, M. (2024). Carboxypeptidase Inhibitor LXN Expression in Endometrial Tissue Is Menstrual Cycle Phase-Dependent and Is Upregulated in Endometriotic Lesions. Genes. 15(8), 1086. https://doi.org/10.3390/genes15081086

Journal articles are reprinted with permission from copyright holders. *Joint first authorship.