Pathogenetic mechanisms of endometrial hyperplasia in women of reproductive age

Abstract

Objective. To analyze pathogenetic mechanisms underlying the development of endometrial hyperplasia in women of reproductive age. Patients and methods. We have examined 143 women of reproductive age with endometrial hyperplasia (EH). Study participants were divided into three groups: Group I included EH patients without atypia; Group II included patients with atypical hyperplasia of the endometrium; Group III (control group) comprised 56 women with abnormal uterine bleeding, in whom we excluded adenomyosis, uterine fibroids, endometrial hyperplasia, endometrial cancer, and iatrogenic causes of uterine bleeding. Genomic DNA was isolated using phenol-chloroform extraction. Real-time polymerase chain reaction (RT-PCR) was used to detect microRNA-210, -18a, -221, and -222. The detection of tumor pyruvate kinase M2 was performed using the ScheBo® Tumor M2-PK kit designed for quantitative assessment of this metabolic cancer marker in plasma and endometrial tissue samples. Results. Significant risk factors triggering the pathogenetic mechanism of EH development in reproductive age include extragenital disorders (obesity, thyroid diseases, diseases of the urinary system, hypertension) and gynecological diseases (pelvic inflammatory diseases, adenomyosis, benign breast dysplasia, uterine fibroids). Alterations affecting estrogen receptors lead to changes in microRNA messengers, which, in turn, affect target genes and cause changes in the adaptive abilities of the cell. Expression of pyruvate kinase M2 in this chain confirms proapoptotic changes in the cell and the risk of its atypia. Conclusion. The pathogenesis of EH is based on the following factors: polymorphism of the ERS1 and PRG genes, increased expression of miRNA-210, -18a, and -222, decreased expression of miRNA-221, and overexpression of pyruvate kinase M2. Key words: endometrial hyperplasia, miRNA, pyruvate kinase M2, progesterone receptors, estrogen receptors