Role of WNT4, HOXA10 and TWIST1 genes in the pathogenesis of external genital endometriosis and uterine leiomyoma

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Abstract

BACKGROUND: Uterine leiomyoma and endometriosis are the most common gynecological diseases in women of reproductive age. A number of data indicate that there are common elements in the pathogenesis of these hyperproliferative conditions. This article is devoted to comparative analysis of the role of the WNT4, HOXA10 and TWIST1 genes in the development of uterine leiomyoma and external genital endometriosis.

AIM: The aim of this study was to evaluate the frequency of polymorphic variants rs7521902 (WNT4) and rs4721745 (TWIST1) in patients with uterine leiomyoma, external genital endometriosis and in the comparison group; to determine the frequency of rare allelic variants of the HOXA10 gene in patients with external genital endometriosis; and to study the expression of these genes in the endometrium in patients with uterine leiomyoma, EGE and in the comparison group.

MATERIALS AND METHODS: The polymorphic variants of the WNT4 and TWIST1 genes were studied by real-time PCR in patients with external genital endometriosis, uterine leiomyoma and in the comparison group. In patients with EGE and women in the comparison group, the second exon of the HOXA10 gene was sequenced. Real-time PCR with reverse transcription analysis of the expression of the WNT4, TWIST1 and HOXA10 genes in endometrial samples from the patients of the study groups was performed.

RESULTS: The frequencies of polymorphic variants rs7521902 (WNT4) and rs4721745 (TWIST1) in patients with uterine leiomyoma, external genital endometriosis and in the comparison group did not differ significantly. Minor alleles of the HOXA10 gene were not identified in patients with external genital endometriosis. Expression of the WNT4 gene in the endometrium of patients with external genital endometriosis was independent of menstrual cycle phase and was reduced by 1.9 times compared to the endometrium of women with uterine leiomyoma. Expression of the HOXA10 gene in the endometrium of endometriosis patients on days 20-23 of the menstrual cycle was significantly reduced compared to the women in the comparison group. Expression of the TWIST1 gene was not altered in the endometrium of patients with uterine leiomyoma and external genital endometriosis.

CONCLUSIONS: We did not identify associations of the studied polymorphic variants of the WNT4 and TWIST genes and minor variants of the HOXA10 gene with uterine leiomyoma and external genital endometriosis. The expression of the WNT4 and HOXA10 genes is reduced in the endometrium in patients with external genital endometriosis, but not in women with uterine leiomyoma. Changes in expression patterns of the studied genes in the endometrium differ significantly in these two diseases.

About the authors

Olga V. Malysheva

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott; Institute of Physiology named after I.P. Pavlov

Author for correspondence.
Email: omal99@mail.ru
ORCID iD: 0000-0002-8626-5071

Cand. Sci. (Biol.)

Russian Federation, Saint Petersburg

Arseny S. Molotkov

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

Email: arseny.molotkov@gmail.com
ORCID iD: 0000-0003-3433-3092
SPIN-code: 6359-6472

Cand. Sci. (Med.)

Russian Federation, Saint Petersburg

Natalya S. Osinovskaya

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott; North-Western State Medical University named after I.I. Mechnikov

Email: natosinovskaya@mail.ru
ORCID iD: 0000-0001-7831-9327
SPIN-code: 3190-2307

Cand. Sci. (Biol.)

Russian Federation, Saint Petersburg

Natalya Yu. Shved

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott; City Hospital No. 40

Email: natashved@mail.ru
ORCID iD: 0000-0001-6354-9226
SPIN-code: 8276-1720

Cand. Sci. (Biol.)

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
Scopus Author ID: 7801562649
ResearcherId: P-2183-2014

MD, Dr. Sci. (Med.), Professor, Professor of the Russian Academy of Sciences

Russian Federation, Saint Petersburg

Vladislav S. Baranov

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

Email: baranov@vb2475.spb.edu
ORCID iD: 0000-0002-6518-1207
SPIN-code: 9196-7297

MD, Dr. Sci. (Med.), Professor, Corresponding Member of the Russian Academy of Sciences, Honored Scientist of the Russian Federation

Russian Federation, Saint Petersburg

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2. Figure. Expression of the HOXA10, TWIST1, and WNT4 genes in the endometrium in the external genital endometriosis group, uterine leiomyoma group, and control group 2 by days of the menstrual cycle: LM, uterine leiomyoma; EM, external genital endometriosis; contr, control group 2. The figures correspond to the days of the menstrual cycle

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