Role of Vascular Endothelial Cell Growth Factor on Pathophysiology of Uterine Adenomyosis

Background: Uterine adenomyosis is defined as the presence of ectopic endometrial tissue in the myometrium of the uterus and is a known cause of chronic pelvic pain, heavy menstrual bleeding, and subfertility. However, its pathogenesis is not completely established. Several reports have suggested that vascular endothelial cell growth factor (VEGF) may be associated with the progression of adenomyosis. The goal of this study was to evaluate the role of VEGF on pathophysiology of uterine adenomyosis by comparing expression of VEGF in the same uterus and in the endometrium and myometrium, with patients’ adenomyosis. Methods: We analyzed 22 premenopausal patients with a focal type of uterine adenomyosis who received an adenomyomectomy between December 2019 and April 2020 at our hospital. All patients were preoperatively treated with gonadotropin-releasing hormone(GnRH) analogs. During these surgeries, samples were obtained from the uterus of each patient which included the adenomyosis lesion, the myometrium without adenomyosis, and endometrial tissue. Immunohistochemistry stain of VEGF and real-time polymerase chain reaction (RT-PCR) of VEGF expression were compared for each of three points in the uterus. We also compared microvascular density in the adenomyosis lesion between the ectopic endometrial gland and myometrial stroma. Results: VEGF expression was found to be increased in adenomyotic lesions and myometrium compared with the eutopic endometrium (p < 0.0001). In addition, RT-PCR indicated higher VEGF expression in the myometrial and adenomyosis tissues than in the eutopic endometrium (p < 0.05). In each patient, a comparison of microvascular density (MVD) measurements of the eutopic endometrium with an endometrial component and stroma in the adenomyosis tissue indicated a significant increase in the stroma comprising the myometrium (p = 0.02). Conclusions: VEGF contributes to the progression of uterine adenomyosis and may be more strongly activated in the stromal component of the myometrium than in the endometrial (eutopic or ectopic) component of the adenomyosis in the same uterus. This suggests that VEGF plays a significant role in the muscular component of the endometrium during the progression of adenomyosis.