The role of <i>WNT</i> and <i>HOXA</i> signaling cascades in the pathogenesis of adenomyosis

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 512 day of the menstrual cycle (proliferative phase) or 2024 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.