The Role of NF-κB in Endometrial Diseases in Humans and Animals: A Review

Abstract

The expression of genes of various proinflammatory chemokines and cytokines is controlled, among others, by the signaling pathway of the nuclear factor kappaB (NF-κB) superfamily of proteins, providing an impact on immune system functioning. The present review addresses the influence and role of the NF-κB pathway in the development and progression of most vital endometrial diseases in human and animal species. Immune modulation by NF-κB in endometritis, endometrosis, endometriosis, and carcinoma results in changes in cell migration, proliferation, and inflammation intensity in both the stroma and epithelium. In endometrial cells, the NF-κB signaling pathway may be activated by multiple stimuli, such as bacterial parts, cytokines, or hormones binding to specific receptors. The dysregulation of the immune system in response to NF-κB involves aberrant production of chemokines and cytokines, which plays a role in endometritis, endometriosis, endometrosis, and endometrial carcinoma. However, estrogen and progesterone influence on the reproductive tract always plays a major role in its regulation. Thus, sex hormones cannot be overlooked in endometrial disease physiopathology. While immune system dysregulation seems to be NF-κB-dependent, the hormone-independent and hormone-dependent regulation of NF-κB signaling in the endometrium should be considered in future studies. Future goals in this research should be a step up into clinical trials with compounds affecting NF-κB as treatment for endometrial diseases.

The Association between Endometriosis and Obstructive Müllerian Anomalies

“…Other risk factors for endometriosis in adolescence than obstructive Müllerian anomalies is positive family history, early menarche, lean body size, low birth weight, intense physical activity and passive smoking increase, which is not quite similar to endometriosis in adults [ 7 ]. Although retrograde menstruation is the main theory of the development of endometriosis, there are other mechanisms like coelomic metaplasia, implantation through the blood or lymphatic vessels, or differentiation from blood cells, hormonal regulation of inflammatory responses, and failure of the immune system [ 2 , 14 , 15 , 16 ]. Neonatal uterine bleeding (NUB) is one of the explanations for endometriosis developing in adolescents.…”

17β‐Estradiol mediates TGFBR3/Smad2/3 signaling to attenuate the fibrosis of TGF‐β1‐induced bovine endometrial epithelial cells via GPER

“…Numerous studies have shown that E2 levels in peripheral circulation are inversely correlated with endometritis prevalence (Wu et al, 2018). It has been reported that the uterus is susceptible to infections/inflammation (endometritis) with the decreasing of blood estrogens concentration and is resistant to infections/ inflammation (endometritis) with the increase of blood estrogens concentration (Zdrojkowski et al, 2023). In addition, it has been shown that disruption of estrogen secretion in endometritis (Green et al, 2011;Zralý et al, 1989).…”

The Importance of Natural Antioxidants in Female Reproduction

“…The overproduction of ROS is an important inducer of chronic NF-κB-mediated inflammatory responses [ 20 ] which can trigger cells into pathologies. Under physiological conditions, the NF-κB subunit p65 and progesterone receptor are mutually repressed [ 21 ]. Progesterone inhibits the NF-κB-induced pro-inflammatory factors in endometriotic cells [ 18 , 21 ].…”

“…Under physiological conditions, the NF-κB subunit p65 and progesterone receptor are mutually repressed [ 21 ]. Progesterone inhibits the NF-κB-induced pro-inflammatory factors in endometriotic cells [ 18 , 21 ]. High mobility group box-1 (HMGB-1) activates NF-κB via binding to its TLR4 (Toll-like receptor 4) receptor and induces inflammatory responses with sustained OS [ 22 ].…”

“…On the other hand, in OS conditions ( Figure 1 ) ROS has a role in the regulation of NF-κB signaling as well as Nrf2 signaling, resulting in abnormal bleeding and uncontrolled apoptosis [ 14 , 21 , 26 ] in pathological processes and diseases such as endometriosis, polycystic ovary syndrome (PCOS), and tubal and idiopathic infertility [ 27 , 28 , 29 ]. During pregnancy, increased placental OS can trigger pregnancy-related problems such as pre-eclampsia, intrauterine growth restrictions, gestational diabetes mellitus, or premature birth [ 30 ].…”