Role of insulin and insulin-like growth factor I receptor expression in the pathogenesis of genital endometriosis

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Abstract

BACKGROUND: Growth factors play an important role in the pathogenesis of genital endometriosis. Insulin and insulin-like growth factors are involved in mitosis and differentiation in the endometrium during the menstrual cycle and early pregnancy, and are likely to indirectly affect the invasion of the endometrium during retrograde menstruation and the development of pain syndrome in endometriosis. However, the available literature data on insulin-like growth factors and insulin in the endometrium and endometrioid heterotopies in patients with genital endometriosis are scarse and contradictory.

AIM: The aim of this study was to investigate the expression of insulin receptors and insulin-like growth factor I receptors in the eutopic endometrium and endometrioid heterotopies of patients with genital endometriosis.

MATERIALS AND METHODS: This cross-sectional study included immunohistochemical analysis of surgical material obtained from two groups of women in the proliferative phase of the menstrual cycle: patients with endometriosis who received surgical treatment (endometrium and endometrioid heterotopies) and patients without endometriosis who were examined due to infertility (endometrium). The study also included investigation of carbohydrate metabolism (glucose tolerance test) and determination of blood serum insulin-like growth factor I, insulin and sex hormone levels. The material was stained to detect the expression of insulin receptors and insulin-like growth factor I receptors. Then, the relative area and optical density of the receptor expression were determined and the obtained data were analyzed statistically.

RESULTS: We analyzed the examination results of 131 women matched in age and weight and height characteristics: 101 patients with genital endometriosis and 30 patients in the control group. Carbohydrate metabolism was characterized by a 2.1-fold increase in glucose-stimulated insulin secretion in patients with genital endometriosis compared with the control subjects. The blood level of insulin-like growth factor I did not differ in the study groups. Statistically significant differences in receptor expression were obtained between the groups. In the endometrium of patients with genital endometriosis, the optical density of insulin receptors was lower (p = 0.007) and the expression of insulin-like growth factor I receptors higher (p = 0.002) compared to the endometrium of the control subjects. The median values of insulin receptor expression in endometrioid heterotopies were decreased compared to the endometrium of the control group (p < 0.001). The expression of insulin-like growth factor I receptors in endometrioid heterotopies was reduced compared to the endometrium of the same patients (p < 0.001).

CONCLUSIONS: The data obtained indicate significant features in the functioning of the insulin / insulin-like growth factor I system in patients with genital endometriosis: glucose-stimulated insulin secretion and relative endometrial insulin resistance due to the decreased expression of insulin receptors and the increased expression of insulin-like growth factor I receptors in the endometrium.

About the authors

Margarita S. Florova

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

Author for correspondence.
Email: fm.sergeevna@gmail.com
ORCID iD: 0000-0003-4569-3827
SPIN-code: 1480-7599
ResearcherId: P-3005-2017
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

Natalya N. Tkachenko

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

Email: liberin@mail.ru
ORCID iD: 0000-0001-6189-3488
SPIN-code: 9633-6701
ResearcherId: K-1734-2018

Cand. Sci. (Biol.)

Russian Federation, Saint Petersburg

Gulrukhsor Kh. Tolibova

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

Email: gulyatolibova@yandex.ru
ORCID iD: 0000-0002-6216-6220
SPIN-code: 7544-4825
Scopus Author ID: 23111355700
ResearcherId: Y-6671-2018

MD, Dr. Sci. (Med.)

Russian Federation, Saint Petersburg

Tatyana G. Tral

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

Email: ttg.tral@yandex.ru
ORCID iD: 0000-0001-8948-4811
SPIN-code: 1244-9631
Scopus Author ID: 37666260400

MD, Cand. Sci. (Med.)

Russian Federation, Saint Petersburg

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2. Fig. 1. Expression of insulin receptors (relative area, %) in the endometrium of patients in the EGE and control groups and in endometrioid heterotopia. EGE, external genital endometriosis

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3. Fig. 2. Expression of insulin receptors in the endometrium of a patient with endometriosis (a) and in the endometrium of a patient without endometriosis (b). × 400

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4. Fig. 3. Expression of insulin-like growth factor 1 (IGF-1) receptors (relative area, %) in eutopic endometrium of the external genital endometriosis (EGE) group and control group, and in endometrioid heterotopias

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5. Fig. 4. Expression of insulin-like growth factor 1 receptors in the endometrium of a patient with endometriosis (a) and in the endometrium of a patient without endometriosis (b). × 400

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