Immune Dysregulation in Endometriomas: Implications for Inflammation

Abstract

The most common manifestation of endometriosis, a condition characterized by the presence of endometrial-like tissue outside of the uterus, is the endometrioma, a cystic ovarian lesion. It is a commonly occurring condition associated with chronic pelvic pain exacerbated prior to and during menstruation, as well as infertility. The exact pathomechanisms of the endometrioma are still not fully understood. Emerging evidence suggests a pivotal role of immune dysregulation in the pathogenesis of endometriomas, primarily influencing both local and systemic inflammatory processes. Among the factors implicated in the creation of the inflammatory milieu associated with endometriomas, alterations in both serum and local levels of several cytokines stand out, including IL-6, IL-8, and IL-1β, along with abnormalities in the innate immune system. While numerous signaling pathways have been suggested to play a role in the inflammatory process linked to endometriomas, only NF-κB has been conclusively demonstrated to be involved. Additionally, increased oxidative stress, both resulting from and contributing to endometriomas, has been identified as a primary driver of both systemic and local inflammation associated with the condition. This article reviews the current understanding of immune dysfunctions in the endometrioma and their implications for inflammation.

Keywords: chocolate cyst; endometrioidal cyst; endometrioma; endometriosis; immune dysregulation; inflammation.

Figure 1

Cytokines and chemokines involved in inflammatory process associated with endometriomas. IL-1β—Interleukin 1β; IL-4—interleukin 4; IL-6—interleukin 6; IL-8—interleukin 8; IL-19—interleukin 19; IL-22—interleukin 22; MCP-1—monocyte chemoattractant protein-1; TNF-α—tumor necrosis factor α; TGF-β1—transforming growth factor β1; VEGF—vascular endothelial growth factor.

Figure 2

The role of oxidative stress and ferroptosis in establishing the inflammation associated with endometriomas. DAMP—damage associated molecular patterns; Fe—iron; IL-8—interleukin 8; LOOH—lipid hydroperoxides; NF-κB—nuclear factor κB; ROS—reactive oxygen species; VEGFA—vascular endothelial growth factor A.

Figure 3

Immune cell abnormalities associated with endometriomas. CD69—cluster of differentiation 69; CD107a—cluster of differentiation 107a/Lysosomal-associated membrane protein 1; IL-4—interleukin 4; IL-13—interleukin 13; ILC—innate lymphoid cells; ILC2—innate lymphoid type-2 cells; M2—M2 polarized macrophages; PD-L1—programmed death 1 ligand; ST2—interleukin 1 receptor-like 1; Tc—cytotoxic T-cells; Treg—regulatory T-cells; TGF-β1—transforming growth factor β1.