Oxidative Stress and Antioxidant Defense in Endometriosis and Its Malignant Transformation

Figure 1

Malignant transformation of endometriosis: a fine-tuned balance between the formation of oxidants and the availability of endogenous antioxidants. Cell-free hemoglobin, heme, and iron massively released into the endometriotic cyst fluid space during menstruation are prone to autoxidation and may spontaneously convert oxyHb to metHb. ROS () are continuously generated by the autoxidation of hemoglobin. Iron derivatives also stimulate Fenton reaction, contributing to the generation of ROS () in endometriotic cyst. Furthermore, hemoglobin and heme activate expression of a variety of antioxidant genes. Heme stimulates antioxidant HO-1 gene expression through direct binding to Bach1 or induction of NRF2 gene. Antioxidant is considered to be a double-edged sword. Excess ROS cause cell death. Antioxidants alleviate cell death by scavenging ROS ( and ), allowing for increased cell survival and then carcinogenesis.