Molecular and Clinical Insights on the Complex Interaction between Oxidative Stress, Apoptosis, and Endobiota in the Pathogenesis of Endometriosis

Abstract

Endometriosis (EMS) remains, to date, an intriguing and debilitating gynecological disorder that possesses a multifactorial substrate. Recent studies with the objective of elucidating its etiology highlighted the antagonistic effect of EMS on a multiple of processes involved in homeostasis. Although the current oxidative biomarkers clearly reveal the consequences induced by EMS, its implication in the associated inflammatory reactions could be much more complex. Besides the overproduction of reactive oxygen species (ROS) that leads to an exacerbated oxidative response, it also changes the normal expression of several pro-inflammatory modulators, reflected by the fluctuating activity of several pro- and anti-apoptotic mediators whose expression is impaired. In light of this topic, several studies elucidate the involvement of apoptosis in EMS, being brought controversial findings, even reports with no significant change. Further, some authors reported an abnormal expression of multiple genes that are crucial for the overall functionality of the female reproductive system. Cumulatively, it seems that the subsequent oxidative imbalance and apoptosis process impairment could further disrupt the normal removal of unnecessary biological products. Based on all gathered evidence, we could argue that the related stress state could determine human endobiota impairment, which could further participate in the inflammatory and main antioxidant enzyme changes occurring in EMS. Moreover, a correlation between endobiota integrity, inflammation, and oxidative stress (OS) was suggested in relation to the possible predisposition to pathogen determined infections.

Therapeutic effects of L‐arginine, L‐carnitine, and mesenchymal stem cell‐conditioned medium on endometriosis‐induced oocyte poor quality in an experimental mouse model

“…Our result showed a notable increase in nitro‐oxidative stress and reduction in TAC levels in EMS‐induced mouse plasma compared to the control group. This is in line with recent studies which revealed that EMS induced an increase in the levels of ROS and NOS in plasma and peritoneal fluid 2,27,28 . Moreover, the peritoneal fluid of patients with EMS showed low levels of ascorbic acid and glutathione peroxidase (GPx) 26,29 .…”

“…Normally, ROS are secondary messengers for cellular signaling that play a critical role in mediating folliculogenesis, meiosis, ovulation, and embryonic development 26 . However, the overabundance of ROS will trigger oxidative stress and may cause a series of reproductive diseases such as EMS 2,26 . Our result showed a notable increase in nitro‐oxidative stress and reduction in TAC levels in EMS‐induced mouse plasma compared to the control group.…”

“…However, treatment options for EMS remain a controversial issue 1,3 . Some approaches combat oxidative stress in EMS, and evidence suggests that antioxidants might be beneficial to these patients 2,3 . In the current study, for the first time, we explored the comparative alleviative effects of LA, LC, and BMSC‐CM on EMS‐induced oxidative stress and impaired oocyte developmental capacity in vivo and in vitro.…”

“…1,3 Some approaches combat oxidative stress in EMS, and evidence suggests that antioxidants might be beneficial to these patients. 2,3 In the current study, for the first time, we explored the comparative alleviative effects of LA, LC, and BMSC-CM on EMS-induced oxidative stress and impaired oocyte developmental capacity in vivo and in vitro. According to our results, induced EMS in a mouse model was associated with reduced oocyte quality and impaired oocyte and embryo development.…”

“…Endometriosis (EMS) is an estrogen-dependent reproductive condition in which endometrial tissue is found outside the uterus and present in 10%-15% of women of reproductive age. 1,2 EMS seriously impacts the quality of life through pelvic pain, dyspareunia, dysmenorrhea, painful defecation, and sub/infertility. 3 Assisted reproductive techniques (ART) have been applied to address EMS-sub/ infertility, and 35%-50% of infertile women undergoing in vitro fertilization (IVF) are impacted by EMS.…”