Peritoneal immune microenvironment of endometriosis: Role and therapeutic perspectives

Abstract

Endometriosis, an estrogen-dependent chronic inflammatory disease characterized by the growth of endometrium-like tissues outside the uterine cavity, affects 10% of reproductive-age women. Although the pathogenesis of endometriosis is uncertain, it is widely accepted that retrograde menstruation results in ectopic endometrial tissue implantation. Given that not all women with retrograde menstruation develop endometriosis, immune factors have been hypothesized to affect the pathogenesis of endometriosis. In this review, we demonstrate that the peritoneal immune microenvironment, including innate immunity and adaptive immunity, plays a central role in the pathogenesis of endometriosis. Current evidence supports the fact that immune cells, such as macrophages, natural killer (NK) cells, dendritic cells (DCs), neutrophils, T cells, and B cells, as well as cytokines and inflammatory mediators, contribute to the vascularization and fibrogenesis of endometriotic lesions, accelerating the implantation and development of ectopic endometrial lesions. Endocrine system dysfunction influences the immune microenvironment through overexpressed estrogen and progesterone resistance. In light of the limitations of hormonal therapy, we describe the prospects for potential diagnostic biomarkers and nonhormonal therapy based on the regulation of the immune microenvironment. Further studies are warranted to explore the available diagnostic biomarkers and immunological therapeutic strategies for endometriosis.

Vitamin D and reproductive disorders: a comprehensive review with a focus on endometriosis

“…Oestrogens are crucial for the growth of endometrial cells, and environmental factors like pesticides and toxicants may contribute to abnormal cell development in women with endometriosis by impacting the production and breakdown of oestradiol [ 166 ]. An oestrogenic microenvironment is established close to endometriotic lesions due to the local accumulation of oestradiol [ 167 ]. A network of genes including greb1, myc, and ccnd1 that govern cell mitogenesis is activated when there are high local concentrations of oestradiol and overexpression of estrogen receptor alpha (ERα) and ERβ [ 168 ].…”

Immune pathway through endometriosis to ovarian cancer

“…In addition to the intricate interplay involving macrophages and the aforementioned mechanisms, it is essential to address the role of fibrosis in this context. In this sense, TGF-β secreted by M2 macrophages induces fibrosis, as it promotes the differentiation of fibroblasts into myofibroblasts and stimulate the synthesis of collagen and fibronectin[ 81 - 83 ]. On the other hand, Barcz et al [ 84 ] suggests that increased levels of VEGF are negatively associated to endometriosis-related pelvic fibrotic adhesions.…”

“…Macrophages also play a role in neurogenesis and, consequently, in the onset of endometriosis-associated pain[ 85 ]. Overall, nerve fibers originating from endometriotic lesions have the capacity to secrete chemokines such as CCL2 and CSF-1, which, as previously discussed, are pivotal in the recruitment of macrophages[ 81 , 86 ]. As a result, macrophages release neurotrophic factors, including brain-derived neurotrophic factor and neurotrophin-3, thus contributing to the heightened sensitivity and pain experienced by individuals with endometriosis[ 86 ].…”

DLK1 as a Potential Biomarker and shows NOTCH signaling could be the potential target for Endometriosis: A Machine Learning Approach

“…One of the hallmarks of endometriosis is the dysregulation of the immune system, which contributes to the establishment, maintenance, and growth of ectopic endometrial lesions. Several studies have shown that endometriosis is associated with altered immune cell populations, cytokine pro les, and in ammatory responses in the peritoneal cavity and systemic circulation (4). Moreover, endometriosis lesions exhibit features of immune evasion and resistance to apoptosis, similar to cancer cells.…”