Unraveling the pathogenic mechanisms behind uterine adenomyosis development and symptoms

Adenomyosis is a benign uterine disease causing chronic pelvic pain, heavy menstrual periods and infertility in as many as 20% of gynecology patients worldwide. Nevertheless, its pathogenesis is not yet fully understood and currently available treatments remain limited and inefficient. The present thesis sought to investigate the mechanisms behind adenomyosis development and symptoms, looking to improve clinical management of the condition. We initially demonstrated the key role of macrophages, found to accumulate in uteri of adenomyosis patients and contribute to the pathogenesis by promoting collective cell migration in endometrial cells. We further explored the underlying causes of adenomyosis-related infertility, confirming impaired endometrial receptivity and decidualization as crucial mechanisms leading to poor reproductive outcomes in these patients. Finally, we developed a novel advanced in vitro model of endometrium, known as endometrial assembloids, with the potential to mimic disease-specific traits and thereby aid future research into adenomyosis pathogenesis and therapeutic responses.