Inflammation-driven epigenetic memory in infertility and chronic endometritis

Chronic endometritis (CE) is a persistent, low-grade inflammatory condition of the endometrium, typically caused by microbial infections. CE is often asymptomatic, leading to frequent underdiagnosis. It is frequently identified during the assessment of causes for infertility. Even after resolving the infectious etiology by antibiotic treatment, infertility persists in a number of patients. Emerging evidence from chronic inflammatory diseases affecting epithelial tissues, e.g., in the gut, suggests that inflammatory conditions can induce long-lasting epigenetic changes, e.g., in innate immune cells. Notably, tissues outside the immune system can also retain memory of inflammatory events and environmental insults via epigenetic modifications. This review summarizes how epigenetic changes can affect endometrial function, drawing on current knowledge of CE. It also discusses how inflammation prompts these changes. We propose that persistent epigenetic memory in both immune and non-immune endometrial cells plays a crucial role in sustaining CE-associated adversities, such as infertility. Future research should focus on pinpointing specific epigenetic patterns in CE and exploring how inflammation-induced memory leads to cellular dysfunction in the endometrium. Understanding these mechanisms will advance CE diagnosis and open doors to new treatment options for infertility, focusing on reversing the inflammatory memory retained upon treatment of CE.