Pathogenetic Mechanisms of Deep Infiltrating Endometriosis

Abstract

Endometriosis is a benign gynecologic disease, affecting women of reproductive age associated with chronic pelvic pain, dysmenorrhea, dyspareunia and infertility. Ovarian endometrioma (OMA), superficial peritoneal endometriosis (SPE), and deep infiltrating endometriosis (DIE) are, till now, recognized as major phenotypes. The discussion is to know whether they share the same pathogenetic mechanisms. Till today, DIE is recognized as the most severe clinical form of endometriosis and has a complex clinical management. The DIE lesions have been considered in the present article, without distinguishing between the anterior (bladder) or the posterior (vagina, uterosacral ligaments, rectum, and ureter) compartment. The present knowledge indicates that hormonal function (estrogen and progesterone receptors) and immunological factors, such as peritoneal macrophages, natural killer cells, and lymphocytes, are critically altered in DIE. The aggressive behavior of DIE may be explained by the highly decreased apoptosis (nuclear factor kappa-light-chain-enhancer of activated B cells [NF-kB], B-cell lymphoma 2 [Blc-2], and anti-Mullerian hormone) and by the increased proliferation activity related to oxidative stress (NF-kB, reactive oxygen species, extracellular regulated kinase (ERK), advanced oxidation protein product). Invasive mechanisms are more expressed (matrix metalloproteinases and activins) in DIE in comparison to the OMA and SPE. Correlated with the increased invasiveness are the data on very high expression of neuroangiogenesis (nerve growth factor, vascular endothelial growth factor, and intercellular adhesion molecule) genes in DIE. Therefore, at the present time, several of the DIE pathogenetic features result specific in comparison to other endometriosis phenotypes, pleading for the existence of a specific entity. These evidence of specific pathogenetic features of DIE may explain the more severe symptomatology related to this form of endometriosis and suggest possible future target medical treatments.

Euterpe oleracea Extract (Açaí) Is a Promising Novel Pharmacological Therapeutic Treatment for Experimental Endometriosis

“…High levels of ROS are generated in endometriosis and induce cell damage and proliferation [61], which supports the important role of peritoneal macrophages in the secretion of pro-inflammatory/proangiogenic cytokines [56,62]. Our findings demonstrated that the presence of F4/80-positive macrophages and NO concentrations were higher in endometriotic lesions and statistically reduced in animals treated with açaí.…”

Cancer-Associated Mutations in Endometriosis without Cancer

“…Deep infiltrating endometriosis is characterized by nodules that locally invade pelvic structures, producing symptoms such as painful intercourse (deep dyspareunia) and painful bowel movements (dyschezia). 5 Progestin-based hormonal therapy and gonadotropin-releasing hormone analogues have become the standard treatments; however, many patients have unacceptable systemic adverse effects in association with either or both treatments. 1,6 Moreover, not all women with endometriosis have a response to hormonal therapy, particularly those who have deeply infiltrating disease.…”

‘Omic’ high-throughput technologies in research on pathogenesis of endometriosis: a Review

“…Гете-рогенность заболевания отражает различия в уровне экспрессии генов, связанных с гипоксией и ангиоге-незом, предполагая, что такое состояние может играть активную роль в развитии заболевания. Зна-чительные различия, наблюдающиеся между DIE и OMA, подтверждают идею, что DIE и OMA являются двумя разными проявлениями эндометриоза [45]. Различные фенотипы эндометриоза показывают разный уровень экспрессии генов, связанных с ги-поксией и ангиогенезом, поддерживая гипотезу, что такие состояния могут способствовать не только раз-витию эндометриоза, но и его началу [30].…”