Endometriosis: current challenges in modeling a multifactorial disease of unknown etiology

Endometriosis is a chronic inflammatory hormone-dependent condition associated with pelvic pain and infertility, characterized by the growth of ectopic endometrium outside the uterus. Given its still unknown etiology, treatments usually aim at diminishing pain and/or achieving pregnancy. Despite some progress in defining mode-of-action for drug development, the lack of reliable animal models indicates that novel approaches are required. The difficulties inherent to modeling endometriosis are related to its multifactorial nature, a condition that hinders the recreation of its pathology and the identification of clinically relevant metrics to assess drug efficacy. In this review, we report and comment endometriosis models and how they have led to new therapies. We envision a roadmap for endometriosis research, integrating Artificial Intelligence, three-dimensional cultures and organ-on-chip models as ways to achieve better understanding of physiopathological features and better tailored effective treatments.