Oxidative stress in the pelvic cavity and its role in the pathogenesis of endometriosis

Abstract

Endometriosis is a disorder associated with a general inflammatory response in the peritoneal cavity. Oxidative stress is a potential factor involved in the pathophysiology of this disease, and reactive oxygen species (ROS) are implicated in this process. Indeed, in healthy individuals, ROS and antioxidants are in balance, but when balance is tipped toward an overabundance of ROS, oxidative stress occurs and can impact the entire reproductive lifespan of a woman. Reactive oxygen species are intermediaries produced by normal oxygen metabolism but are known to have deleterious effects. Excessive release of ROS induces cellular damage and alters cellular function by regulating protein activity and gene expression, leading to harmful effects. To protect themselves, cells have developed antioxidant systems to limit production of ROS, inactivate them, and repair cell damage. Understanding of the control of hemoglobin, heme, and iron-induced redox balance in endometriosis led us to propose a number of hypotheses to explain why oxidative stress is induced in case of pelvic endometriosis. Erythrocytes, apoptotic endometrial tissue, and cell debris transplanted into the peritoneal cavity by menstrual reflux and macrophages have all been cited as potential inducers of oxidative stress. Erythrocytes are likely to release pro-oxidant and proinflammatory factors, such as hemoglobin and its highly toxic by-products heme and iron, into the peritoneal environment. Iron and heme are essential to living cells, but unless appropriately chelated, free iron, and to a lesser extent heme, play a key role in the formation of deleterious ROS.

Cancer driver mutations in endometriosis: Variations on the major theme of fibrogenesis

“…As ectopic endometrium experiences cyclic bleeding, cell‐free hemoglobin and its highly toxic by‐products heme and iron are released from erythrocytes in and around lesions. Lysis of erythrocytes by macrophages results in iron overload, inducing iron‐mediated damage, oxidative injury and inflammation and oxidative stress . Consistently, granulosa cells from patients with infertility and endometriosis exhibit more signs of severe oxidative DNA damage when compared with cells from other patients with infertility .…”

“…Lysis of erythrocytes by macrophages results in iron overload, inducing iron-mediated damage, oxidative injury and inflammation and oxidative stress. 375 Consistently, granulosa cells from patients with infertility and endometriosis exhibit more signs of severe oxidative DNA damage when compared with cells from other patients with infertility. 377 Expression levels of 8-hydroxydeoxyguanosine (8-Oh-dG), a sensitive indicator of DNA damage resulting from oxidative stress, are reported to be significantly higher in samples of normal ovarian cortex surrounding endometriotic cysts.…”

“…Oxidative stress has been well‐documented to be involved in the pathophysiology of endometriosis . DNA is particularly vulnerable to the damaging effect of reactive oxygen species (ROS), as are other biomolecules.…”

“…Oxidative stress has been well-documented to be involved in the pathophysiology of endometriosis. 375 DNA is particularly vulnerable | 383…”

Endometriosis and risk of embryonic aneuploidy?

“…Indeed, Kitajima et al (4) clearly demonstrated the ''burn-out'' effect on the ovarian reserve induced by the ''toxic'' intraovarian environment and inflammation due to the presence of ovarian endometriomas, leading to increased fibrosis, loss of cortex-specific stroma, vascularization defects, and ultimately, impaired follicular maturation and greater follicular atresia. Moreover, the role of oxidative stress should not be overlooked (5), because excessive release of reactive oxygen species alters cellular function by dysregulating protein activity and gene expression, resulting in harmful effects (5).…”