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

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Abstract

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.

MATERIALS AND METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

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About the authors

Olga V. Malysheva

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Author for correspondence.
Email: omal99@mail.ru
ORCID iD: 0000-0002-8626-5071
SPIN-code: 1740-2691
Scopus Author ID: 6603763549
ResearcherId: O-9897-2014

Cand. Sci. (Biol.)

Russian Federation, Saint Petersburg

Alexandra K. Beganova

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: alexandra.beganova@yandex.ru
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: vi_lena@list.ru
ORCID iD: 0000-0002-6996-8891
SPIN-code: 2811-8730
ResearcherId: D-3422-2017

Cand. Sci. (Biol.)

Russian Federation, Saint Petersburg

Maria A. Shalina

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: amarus@inbox.ru
ORCID iD: 0000-0002-5921-3217
SPIN-code: 6673-2660
ResearcherId: A-7180-2019

MD, Cand. Sci. (Med.)

Russian Federation, Saint Petersburg

Maria 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: m.yarmolinskaya@gmail.com
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 Petersburg

Andrey S. Glotov

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: anglotov@mail.ru
ORCID iD: 0000-0002-7465-4504
SPIN-code: 1406-0090
Scopus Author ID: 7004340255
ResearcherId: E-8525-2015

Dr. Sci. (Biol.)

Russian Federation, Saint Petersburg

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Supplementary files

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2. Fig. 1. Expression of the HOXA10, HOXA11 and WNT4 genes in the proliferative endometrium of patients with adenomyosis and in the control group

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3. Fig. 2. Correlation of the HOXA10 and HOXA11 gene expression levels in the endometrium of patients with adenomyosis (a) and in the control group (b). RQ, relative level of gene expression

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4. Fig. 3. The frequency of increased (4th quartile) expression of the HOXA10/A11 and WNT4 genes in the endometrium of patients with adenomyosis and in the control group. Q — quartile

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