Pathogenesis of endometriosis: the role of initial infection and subsequent sterile inflammation (Review).

Endometriosis is a common type of chronic inflammatory disease with an immunological background. In this review, we aimed to explore the contemporary literature on the infection and sterile inflammation that support the pathogenesis of endometriosis. This article reviews the English‑language literature on inflammatory, environmental, immunological and oxidative factors associated with endometriosis in an effort to identify factors that cause a predisposition to endometriosis. Intrauterine microbes may be critical for the initiation of endometriosis; the initial activation of pathogen recognition receptors by microbial stimuli results in the activation of proinflammatory pathways and innate immunity. In addition to their response to various exogenous pathogen‑associated molecular patterns, Toll‑like receptors (TLRs) also recognize a wide range of endogenous danger‑associated molecular patterns (DAMPs). The increased expression levels of DAMPs may be involved in the subsequent process of nuclear transcription factor‑κB‑dependent sterile inflammation. Oxidative stress, secondary to the influx of iron during retrograde menstruation, is involved in the progression of endometriosis. DAMP‑mediated danger signals and oxidative stress are bidirectional during sterile inflammation (danger signal spiral). This review supports the hypothesis that there are at least two distinct phases of endometriosis development: The initial wave of TLR activation in modulating innate immune responses would be followed by the second big wave of sterile inflammation.