A novel theory implicating hypochlorous acid as the primary generator of angiogenesis, infertility, and free iron in endometriosis

Endometriosis is a chronic inflammatory gynecologic disorder characterized by the presence of endometrial glands and stroma throughout the abdominopelvic cavity, including the surfaces of the ovaries, uterus, fallopian tubes, small and large bowel, and anterior/posterior cul-de-sacs. Research on the pathophysiology of endometriosis has revealed several biologically active proinflammatory mediators, such as myeloperoxidase (MPO), reactive oxygen species, and free iron. The generation of free iron is believed to be driven by high activity of inducible heme oxygenase; however, this does not fully explain the clinical features of endometriosis, such as implantation, hypoxic stress, appearance of lesions, or marked elevations of free iron. Therefore, this review proposes a new theory highlighting that MPO, and subsequently generated hypochlorous acid, may direct the ectopic implantation of endometrial tissue and progression of endometriosis via tissue hypoxia and angiogenesis and modulation of inducible heme oxygenase activity, free iron generation, and increased reactive oxygen species activity. Furthermore, we discuss the pathway in which MPO-hypochlorous acid directly and indirectly impacts the follicular microenvironment and oocyte, contributing to endometriosis-associated infertility. We conclude with the hypothesis that these adverse effects may be attenuated through antioxidant supplementation, such as lycopene or melatonin. (c) 2022 by American Society for Reproductive Medicine.