Current Understanding of and Future Directions for Endometriosis-Related Infertility Research with a Focus on Ferroptosis.

Abstract

To date, the development of therapy for endometriosis and disease-related infertility remains a major challenge. Iron overload caused by periodic bleeding is a hallmark of endometriosis. Ferroptosis is an iron- and lipid-reactive oxygen species-dependent type of programmed cell death that is distinct from apoptosis, necrosis, and autophagy. This review summarizes the current understanding of and future directions for the research and treatment of endometriosis and disease-related infertility, with the main focus on the molecular basis of ferroptosis in endometriotic and granulosa cells. Papers published between 2000 and 2022 in the PubMed and Google Scholar databases were included in this review. Emerging evidence suggests that ferroptosis is closely linked to the pathophysiology of endometriosis. Endometriotic cells are characterized by ferroptosis resistance, whereas granulosa cells remain highly susceptible to ferroptosis, suggesting that the regulation of ferroptosis is utilized as an interventional target for research into the treatment of endometriosis and disease-related infertility. New therapeutic strategies are urgently needed to efficiently kill endometriotic cells while protecting granulosa cells. An analysis of the ferroptosis pathway in in vitro, in vivo, and animal research enhances our understanding of the pathogenesis of this disease. Here, we discuss the role of ferroptosis modulators as a research approach and potential novel treatment for endometriosis and disease-related infertility.