MicroRNAs in Endometriosis: Insights into Inflammation and Progesterone Resistance

Abstract

Endometriosis, a non-malignant gynecological disorder influenced by estrogen, involves the growth of endometrial tissue outside the uterus. Its development includes processes such as inflammation, progesterone resistance, angiogenesis, and cell proliferation. Epigenetic factors, particularly the dysregulation of microRNAs (miRNAs), have emerged as key factors in these mechanisms in endometriosis. This review aims to unveil the intricate molecular processes that control inflammation, progesterone resistance, and miRNA functions in endometriosis. In addition, it provides a comprehensive overview of the current understanding regarding the involvement of miRNAs in the inflammatory aspects of this condition. This synthesis encompasses research investigating the molecular underpinnings of inflammation, along with the biogenesis and roles of miRNAs in endometriosis. Furthermore, it examines human studies and functional analyses to establish the intricate connection between miRNAs, inflammation, and progesterone resistance in the context of endometriosis. The results highlight the significant impact of dysregulated miRNAs on the inflammatory pathways and hormonal imbalances characteristic of endometriosis. Consequently, miRNAs hold promise as potential non-invasive biomarkers and targeted therapeutic agents aimed at addressing inflammation and enhancing the response to progesterone treatment in individuals with endometriosis.

Keywords: endometriosis; inflammation; microRNA; progesterone resistance.

Figure 1

Illustration depicting the cascades of inflammatory processes intertwined with hormonal imbalances in endometriosis. Created with BioRender.com. Abbreviations: IL—interleukin; HNP1–3—human neutrophil peptides 1–3; ENA—epithelial neutrophil-activating peptide; VEGF—vascular endothelial growth factor; ESC—endometrial stromal cells; IFNγ—interferon γ; ER–estrogen receptor; E2—estradiol; E1—estrone; 17β-HSD-2—17β-hydroxysteroid dehydrogenase type 2; PR—progesterone receptor; KAR—killer activating receptor; KIR—killer inhibitory receptor; NF-κB—nuclear factor-κB; TNFα—tumor necrosis factor α; COX-2—cyclooxygenase 2; BDNF—brain-derived neurotrophic factor; NT-3—neurotrophin-3; MMP—matrix metalloproteinase; SHP-2—Src homology region 2-containing protein tyrosine phosphatase-2; PD-1—programmed cell death protein 1; PD-L1—programmed cell death ligand 1; The arrows indicate dysregulation of immune mediators produced by immune cells and steroid hormone imbalances in endometriotic lesion.