Gene Expression Analysis of Extracellular Matrix and Cytokines after Uterine Artery Embolization

Abstract

Arterial embolization of myomas (AEM) is an established option for the conservative treatment of uterine leio-myomas; it treats all present uterine nodules at once, is less invasive than other procedures and effective in controlling symptoms, and does not require long term hospitalizations. Nevertheless, the potential impact on endometrial morphological and functional outcomes after the procedure is still controversial based on reports of endometritis or eventual transient ischemia. This study evaluated endometrial reorganization in uterine leiomyoma patients, before and after AEM, through gene expression analyses of extracellular matrix and cytokines genes in the endometrial tissue. Eight patients with leiomyomas were evaluated before AEM and 6 months after. The examinations included transvaginal pelvic ultrasonography, dosing of the follicle-stimulating hormone, and endometrial biopsy during the second phase of the menstrual cycle. RNA was extracted from endometrial samples, cDNA was synthesized, and applied on PCR array™ plates to evaluate the expression of extracellular matrix (ECM) genes and cytokines and their receptors' genes (CYT). The ECM overexpressed genes were MMP (1, 3, 10, 11, and 14), CTGF1, ICAM1, TBHS1, ITGA2, ITGA3, ITGB3, COL7A1, COL12A, SPP1, and TNC; ADAMTS8 was underexpressed. The CYT overexpressed genes were SPP1, BCL6, CXCL12, IL-8, and CEBPB; CXCL13 and CCL21 were underexpressed. The ECM results showed overexpression of proteases that are responsible for dysfunctions in the ECM, and of genes responsible for adhesion and membrane components. The CYT results showed overexpression of chemokines responsible for endometrial repair, and underex-* Corresponding author. A. Bernardo et al. 936pression of cytokines involved in inflammatory processes in the endometrial tissue. AEM treatment did not negatively affect the endometrial function at 6 months after embolization. This study broadens the knowledge about using a procedure that is relevant to the treatment of leiomyomas and contributes to the establishment of future guidelines for the decision making process for physicians and patients.

Extracellular matrix metalloproteinase expression in endometrial tissue after arterial embolization of myomas

“…The metalloproteinase genes are related to the facilitation of embryonic implantation ( 7 , 8 , 10 , 16 ). In our study, we observed an under-expression of MMP3 6 months post-AEM.…”

“…ECM metalloproteinases (MMP) are involved in matrix rupture during physiological processes such as embryonic development, reproduction, and tissue remodeling. Degradation and remodeling of the ECM are also key events in human reproduction ( 9 , 10 ). Hilario et al ( 11 ) evaluated gene expression related to endometrial receptivity in patients undergoing AEM, concluding that there was under-expression of the LIF , IL-11 , and Hoxa-11 genes, and that the expression of IL-6, claudin-4, Hoxa-10, estrogen, and progesterone receptors in the endometrium did not change significantly after AEM.…”

“…Hilario et al ( 11 ) evaluated gene expression related to endometrial receptivity in patients undergoing AEM, concluding that there was under-expression of the LIF , IL-11 , and Hoxa-11 genes, and that the expression of IL-6, claudin-4, Hoxa-10, estrogen, and progesterone receptors in the endometrium did not change significantly after AEM. Bernardo et al ( 10 ) screened 86 ECM genes and cytokines and found overexpression of some MMPs after AEM. Thus, this study showed MMP changes after AEM.…”