The role of WNT and HOXA signaling cascades in the pathogenesis of adenomyosis

BACKGROUND: Adenomyosis is a common gynecological disease with unknown pathogenesis. The HOXA10, HOXA11 and WNT4 genes may play an important role in the pathogenesis of adenomyosis both at the stage of embryonic development and in the postnatal period. The study of their expression in the endometrium of patients with adenomyosis can expand the understanding of the pathogenesis of this disease. AIM: The aim of this work was to study the peculiarity of the WNT4, HOXA10 and HOXA11 gene expression in the eutopic endometrium of patients with isolated adenomyosis.

The study included 38 women: the main group involved patients with isolated adenomyosis established by ultrasound / magnetic resonance imaging (n = 20) and the control group consisted of healthy patients (n = 18). Endometrial sampling was obtained during surgery or by aspiration biopsy at 5–12 day of the menstrual cycle (proliferative phase) or 20–24 day of the menstrual cycle (secretory phase). The expression of the WNT4, HOXA10 and HOXA11 genes in endometrial samples was assessed by a real-time reverse transcription polymerase chain reaction.

In the proliferative phase endometrial samples of patients with adenomyosis, a significant increase in the WNT4 (of almost two times), HOXA10 and HOXA11 (of one and a half to two times) gene expression levels was shown compared to the control group. In 88% of patients with adenomyosis, there is a significant increase (up to the level of fourth quartile) in the expression of at least one of these genes, such changes being not typical for the endometrium of women in the control group. In the secretory phase endometrial samples, the expression of the studied genes did not differ from the level characteristic of the corresponding groups in the proliferative phase of the cycle.

The aberrant expression of the WNT4, HOXA10 and HOXA11 genes in the endometrium of patients with adenomyosis indicates a significant role of these genes in the development of the disease and infertility associated with adenomyosis.

Full Text About the authors Olga V. Malysheva The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Author for correspondence. Email: [email protected] ORCID iD: 0000-0002-8626-5071 SPIN-code: 1740-2691 Scopus Author ID: 6603763549 ResearcherId: O-9897-2014 Cand. Sci. (Biol.) Russian Federation, Saint PetersburgAlexandra K. Beganova The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Email: [email protected] ORCID iD: 0000-0002-4705-7990 SPIN-code: 2612-9889 Russian Federation, Saint Petersburg Elena S. Vashukova The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Email: [email protected] ORCID iD: 0000-0002-6996-8891 SPIN-code: 2811-8730 ResearcherId: D-3422-2017 Cand. Sci. (Biol.) Russian Federation, Saint PetersburgMaria A. Shalina The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Email: [email protected] ORCID iD: 0000-0002-5921-3217 SPIN-code: 6673-2660 ResearcherId: A-7180-2019 MD, Cand. Sci. (Med.) Russian Federation, Saint PetersburgMaria I. Yarmolinskaya The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott; North-Western State Medical University named after I.I. Mechnikov Email: [email protected] ORCID iD: 0000-0002-6551-4147 SPIN-code: 3686-3605 Scopus Author ID: 7801562649 ResearcherId: P-2183-2014 MD, Dr. Sci. (Med.), Professor, Professor of the Russian Academy of Sciences Russian Federation, Saint Petersburg; Saint PetersburgAndrey S. Glotov The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Email: [email protected] ORCID iD: 0000-0002-7465-4504 SPIN-code: 1406-0090 Scopus Author ID: 7004340255 ResearcherId: E-8525-2015 Dr. Sci. (Biol.) Russian Federation, Saint PetersburgReferences - Antero MF, Ayhan A, Segars J, et al. Pathology and pathogenesis of adenomyosis. 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