Ovarian endometriosis(OEM) is the most common type of endometriosis, but there is still a lack of simple and easy-to-promote animal models. Therefore, it is necessary to establish a feasible animal model of OEM and analyze its pathogenesis. In this study, a novel insertional surgical method was used to construct the OEM rat model. The rat model group's morphology and HE staining revealed a close relationship between the transplanted ectopic tissue and the ovary. Compared to the surgery group and the normal group, the bilateral OEM group's level of Anti-mullerian hormone(AMH) was noticeably lower. There was no discernible difference in the unilateral OEM group's AMH level between the normal and sham operation groups. Serum interleukin-1beta(IL-1β) levels in four groups of rats showed bilateral OEM had the greatest level, followed by unilateral OEM. Compared to the normal group, the two model groups had greater serum levels of IL-1β. According to immunohistochemistry, unilateral OEM had higher Intercellular adhesion molecule 1(ICAM1), Matrix metalloproteinase-9(MMP9), Tumor necrosis factor-α(TNF-a), and IL-1β expression levels than the normal rat endometrium. WB revealed that bilateral and unilateral ectopic tissues had higher levels of MMP9, TNF-a, Vascular endothelial growth factor D and IL-1β expression than normal tissues. Transcriptome research revealed that ectopic tissues had higher pro-inflammatory, immunological, and ectopic endometrial proliferation pathways than normal tissues. The ovaries of unilateral OEM have down-regulated immune and inflammation-related pathways and up-regulated steroid hormones compared to normal ovarian tissue. GSEA enrichment analysis comparisons between rat and human endometriotic tissue revealed that Janus kinase-signal transducer and activator of transcription(JAK-STAT), Nuclear factor-kappa B(NFκB), and Toll-like receptors were up-regulated. The intercalation approach of OEM building used in this work is more akin to the human OEM lesion type. It deserves promotion that modeling is more straightforward and has a higher success rate than the suture approach.

Endometriosis is a chronic inflammatory gynecologic disease characterized by the abnormal implantation of endometrial tissue outside the uterus. The inflammatory microenvironment of endometriosis is dominated by highly migratory endometriotic cells, inflammatory cells, and cytokines. There is no curative treatment other than oral contraceptives, painkillers, and surgery. N-acetyl-L-cysteine (NAC), an anti-inflammatory compound has been identified as a promising agent for endometriosis. However, it is still unclear how NAC interacts with interferon-gamma (IFN-ɣ) and common cytokines in the endometriotic microenvironment. This study aimed to investigate the effects of NAC, alone and in combination with IFN-ɣ and major cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-⍺) on endometriotic cells. For this purpose, we performed a real time-dependent cell impedance assay, Annexin V/PI and ER tracking by flow cytometry, immunofluorescence, western blotting, and metabolomic assays. Our results offered a new insight into the complex relationship between NAC and IFN-ɣ, both of which reduced endometriotic cells' proliferation, induced ER stress and mitochondrial dysfunction. In conclusion, NAC and IFN-ɣ, alter the metabolism of endometriotic cells, leading to endoplasmic reticulum stress and mitochondrial dysfunction. These findings suggest that NAC when combined with IFN-ɣ, has the potential to generate innovative therapeutic modalities for the treatment of endometriosis.

Endometriosis affects about 10 % of women of reproductive age, leading to a disabling gynecologic condition. Chronic pain, inflammation, and oxidative stress have been identified as the molecular pathways involved in the progression of this disease, although its precise etiology remains uncertain. Although mitochondria are considered crucial organelles for cellular activity, their dysfunction has been linked to the development of this disease. The purpose of this review is to examine the functioning of the mitochondrion in endometriosis: in particular, we focused on the mitochondrial dynamics of biogenesis, fusion, and fission. Since excessive mitochondrial activity is reported to affect cell proliferation, we also considered mitophagy as a mechanism involved in limiting disease development. To better understand mitochondrial activity, we also considered alterations in circadian rhythms, the gut microbiome, and estrogen receptors: indeed, these mechanisms are also involved in the development of endometriosis. In addition, we focused on recent research about the impact of numerous substances on mitochondrial activity; some of them may offer a future breakthrough in endometriosis treatment by acting on mitochondria and inhibiting cell proliferation.

Pelvic pain, often associated with endometriosis, significantly affects women's quality of life. This study explored the soluble neural cell adhesion molecules (sNCAM), soluble interleukin 2 receptor α (sIL-2Rα), and IL-2 levels in the serum and peritoneal fluid of infertile women with pelvic pain.

We enrolled 86 infertile women aged 24 to 41 years undergoing diagnostic laparoscopy: 44 women with endometriosis and 42 women who acted as controls. Pain intensity was assessed using the visual analog scale. The soluble molecules were measured using enzyme-linked immunosorbent assay.

Serum and peritoneal sNCAM, sIL-2Rα, and IL-2 levels were statistically significantly higher in women with pelvic pain. Both serum and peritoneal sNCAM levels correlated with visual analog scale scores, indicating a relationship between these markers and pain severity. Elevated peritoneal sIL-2Rα levels were also associated with pelvic pain. Receiver operating characteristic curve analysis showed the potential of serum sNCAM in distinguishing between mild and moderate to severe pain.

Elevated levels of sNCAM, sIL-2Rα, and IL-2 in serum and peritoneal fluid correlate with pelvic pain severity in infertile women, suggesting their involvement in disease pathogenesis and potential as objective biomarkers for pain assessment in endometriosis. Further research is needed to validate these findings for clinical use.

As a complex chronic gynecological disorder characterized by multifaceted etiology involving genetics, environment, immunity and inflammation, endometriosis (EM) has long been a significant concern for women of reproductive age worldwide. This review aimed to comprehensively examine the interplay between epigenetics and oxidative stress (OS) in the pathogenesis of EM. Through the integration of cutting-edge research, the response of OS signals to epigenetic modifications was explored. The microbiome exerts an influence on this causal regulatory relationship, and these mechanisms collectively contribute to the pathophysiology of EM. Specifically, this article highlighted the roles of epigenetics and OS in EM and underscored the importance of the microbiome as a regulatory link. A discussion was also held on the future directions of biomarkers and precision medicine, including the application prospects of epigenetic and OS markers in the diagnosis and treatment decision-making of EM, and innovations in therapeutic strategies like targeting epigenetic modifications and antioxidant therapies. Moreover, this review emphasized the potential of multi-omics integrated analysis to deepen the understanding of the disease, guide future therapeutic strategies and promote personalized medicine.

IL-27 is structurally an immune-enhancing and pleiotropic two-chain cytokine associated with IL-12 and IL-6 families. IL-27 contains two subunits, namely IL-27p28 and EBI3. A heterodimer receptor of IL-27, composed of IL27Rα (WSX1) and IL6ST (gp130) chains, mediates the IL-27 function following the activation of STAT1 and STAT3 signaling pathways. Specifically, IL-27 is identified as augmenting cytokine of immune responses, including Th1 cell differentiation, TCd4 + cell proliferation, and IFN-γ production with the help of IL-12. According to several published studies, due to the pro-inflammatory or anti-inflammatory functions of cytokine related to the biological context in various disorders and diseases, IL-27 has been considered a complex regulator of the immune system. Surprisingly, the dual role of IL-27, the same as the double-edged sword, has also been evidenced in clinical models of various hematological or solid tumors. Predominantly, Il-27 applies anti-tumor functions by inducing the responses of a cytotoxic T lymphocyte (CTL) and Th1 and suppressing the growth, proliferation, angiogenesis, invasiveness, metastasis, and survival of tumor cells. On the other hand, IL-27 may also play a protumor role in cancers and induce tumor progression. The current update study aimed to summarize the protumor anti-tumor and biological functions of IL-27 in different hematological malignancies and solid tumors.

Endometrial glands and stroma can be seen outside the uterine cavity in endometriosis, a gynecological disorder linked to estrogen dependency. Hormonal therapies, surgical excision, and non-steroidal anti-inflammatory drug therapy are among the traditional endometriosis treatments, however, various side effects limit their efficacy. Therefore, it is vital to research complementary and alternative therapeutic modalities to decrease the side effects of conventional therapies. While the search for the best endometriosis treatment continues, the focus is being paid to the assistance provided by polyphenols, notably quercetin. A broad spectrum of health-improving benefits of quercetin includes interactions with endometriosis-related molecular targets such as cell proliferation, apoptosis, invasiveness, inflammation, and oxidative stress. According to already-known research, medicines that mimic the physiological effects of quercetin are good candidates for creating novel endometriosis therapies. This review aims to comprehensively review quercetin's potential as a non-pharmacological treatment for endometriosis by interacting with several cellular and molecular targets.

Endometriosis is a common gynecological condition affecting approximately 10% of women of reproductive age, characterized by the abnormal presence of endometrial-like tissue outside the uterus. Although endometriosis was first described over 300 years ago, its underlying mechanisms remain poorly understood, and accurate, prompt diagnosis continues to be challenging. Currently, there is a lack of effective, non-invasive diagnostic methods, and available treatments often come with significant side effects and high recurrence rates. This has spurred interest in investigating the role of pro- and anti-inflammatory molecules, particularly cytokines, in endometriosis, as these molecules play a key role in its progression by influencing cell growth and differentiation. Previous studies suggest that various cytokines could serve as potential biomarkers for diagnosing endometriosis, as they are detectable in both serum and peritoneal fluid. This review provides an overview of the expression, origin, function, and regulation of specific cytokines in endometriosis, along with a brief discussion on their potential clinical implications for diagnosis. Due to the complexity of endometriosis, a panel of multiple biomarkers may ultimately be necessary for accurate diagnosis. It is essential to consider factors such as patient selection, sample collection, and analytical variability when initiating or evaluating biomarker studies.

To investigate the factors influencing recurrence following laparoscopic conservative surgery in patients with ovarian endometriosis (OEM) and to develop a predictive model.

In this retrospective study, the clinical data from 212 OEM patients who underwent laparoscopic conservative surgery at Suzhou Ninth People's Hospital from May 2013 to December 2021 were meticulously reviewed. According to disease recurrence over a 2-year follow-up period, the patients were divided into a recurrence group and a non-recurrence group. Univariate and multivariate logistic regression analyses were performed to identify factors associated with postoperative recurrence in OEM patients. A nomogram prediction model for postoperative recurrence in OEM patients was constructed using R 3.4.3 software. The discriminative power of the model was assessed using the area under the receiver operating characteristic (ROC) curve (AUC), with goodness of fit evaluated using the H-L goodness-of-fit test and Bootstrap method (self-sampling method). Clinical net benefit was analyzed through decision curve analysis.

Over a two-year follow-up, 36 cases of recurrence were observed, yielding a recurrence rate of 16.98%. Bilateral cysts (OR = 2.257, P = 0.005), high r-ASRM stage (OR = 2.651, P = 0.001), and elevated postoperative TNF-α levels (OR = 3.607, P = 0.004) were identified as risk factors for recurrence after laparoscopic conservative surgery in patients with OEM, while older age (OR = 0.566, P = 0.018) and postoperative adjuvant medication (OR = 0.509, P = 0.016) were protective factors. The nomogram prediction model, based on the above indicators, had an AUC of 0.895 for postoperative recurrence risk in OEM patients, with no overfitting phenomenon indicated by the goodness-of-fit test (χ2 = 1.786, P = 0.987). The Bootstrap validation (1000 samples) showed an average absolute error of 0.018 between predicted and actual probabilities. Decision curve analysis showed that the model effectively predicted a clinically relevant net benefit for postoperative recurrence risk.

A nomogram prediction model incorporating age, cyst distribution, r-ASRM staging, postoperative TNF-α levels, and postoperative adjuvant drugs effectively assesses the recurrence risk in OEM patients.

Numerous factors (including immunological, congenital, hormonal, and morphological disorders) can lead to infertility. In this regard, 3 specific diseases associated with infertility are discussed in this review study (i.e., polycystic ovary syndrome [PCOS], endometriosis [EMS], and unexplained infertility [UI]). PCOS is a common endocrine disorder characterized by chronic low-grade inflammation, and EMS is a benign disease characterized by the presence of ectopic endometrial tissue. UI refers to couples who are unable to conceive for no known reason. Conception and pregnancy are significantly affected by the immune system; in this regard, chemokines and cytokines play important roles in the regulation of immune responses. Patients with PCOS, EMS, and UI have altered cytokine and chemokine profiles, suggesting that dysregulation of these molecules may contribute to infertility in these conditions. Accordingly, the issue of infertility is addressed in this review study, a condition that affects approximately 16% of couples worldwide.

Endometriosis is an estrogen-dependent inflammatory disease, defined by the presence of functional endometrial tissue outside of the uterine cavity. This disease is one of the main gynecological diseases, affecting around 10%-15% women and girls of reproductive age, being a common gynecologic disorder. Although endometriosis is a benign disease, it shares several characteristics with invasive cancer. Studies support that it has been linked with an increased chance of developing endometrial ovarian cancer, representing an earlier stage of neoplastic processes. This is particularly true for women with clear cell carcinoma, low-grade serous carcinoma and endometrioid. However, the carcinogenic pathways between both pathologies remain poorly understood. Current studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers (EAOCs) via pathways associated with oxidative stress, inflammation, and hyperestrogenism. This article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis, specifically focusing on the complex relationship between the immune response to endometriosis and cancer, including the molecular mechanisms and their ramifications. Examining recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.

Endometriosis is a common gynecological condition with a complex physio-pathological background. This study aimed to assess the role of Rubus idaeus leaf extract (RiDE) as a potential therapeutic agent in reducing the size of the endometriotic lesions and modulate the plasma expression of MMP-2, MMP-9, and TGF-β1. The endometriotic lesions were induced in a rat model by the autologous transplant of endometrium. Thirty-six female rats, Wistar breed, with induced endometriosis, were divided into four groups and underwent treatment for 28 days. The CTRL group received 0.5 mL/day of the vehicle; the DG group received 1 mg/kg b.w./day dienogest; the RiDG group received 0.25 mL/kg b.w./day RiDE and the D+RiDG group received 1 mg/kg b.w./day dienogest and 0.25 mL/kg b.w./day RiDE, respectively. Rats' weight, endometriotic lesion diameter and grade, and plasma levels of MMP-2, MMP-9, and TGF-β1 were assessed before and after treatment. The administration of RiDE in association with dienogest vs. dienogest determined a lower weight gain and a reduction in diameter of the endometriotic lesions. RiDE administration restored MMP2 and MMP9 plasma levels to initial conditions. Rubus idaeus extract may help in reducing dienogest-associated weight gain, lower the size of endometriotic lesions, and have anti-inflammatory effects through MMP2 and MMP9 reduction.

Paulownia tomentosa flower polysaccharide (PTFP) from dried cultured P. tomentosa flowers, is widely known for its immunomodulatory activities. Here, PTFP was extracted from Paulownia tomentosa flower using hot water extraction, followed by ethanol precipitation methods. Structural characterization of PTFP was revealed by scanning electron microscope, high-performance anion-exchange chromatography, gel chromatography, ultraviolet and infrared spectral. Meanwhile, adjuvant action of PTFT on the immune responses to classical swine fever vaccine in mice was evaluated to further proclaim the immune regulatory effect of PTFP. The results showed that PTFP was a type of heteropolysaccharide with a dense, rough surface and high molecular weight (667.02 kDa), mainly composed of glucose (30.93%), rhamnose (29.99%), galactose (15.66%), arabinose (6.95%), mannose (5.52%), and xylose (4.80%). The results of gel chromatography suggested that the molecular configuration of PTFP may be a spherical structure. The infrared spectrum results confirmed that the functional groups and chemical bond of PTFP contained -OH, O-H, C-H, C=O, C-O, etc. Moreover, PTFP exhibited obvious immune enhancement effect by improving concanavalin A (ConA), lipopolysaccharide (LPS), and CSFV E2-stimulated splenocyte growth and natural killer cell activity in CSFV-immunized mice. Similarly, the titers of CSFV E2-specific IgG, IgG1, IgG2a, and IgG2b antibodies and IFN-γ and IL-10 levels in CSFV-immunized mice were distinctly increased by PTFP treatment. Overall, PTFP was a macromolecular heteropolysaccharide primarily containing glucose and rhamnose, and possessed the auxiliary effect of immune enhancement on the immune responses to classical swine fever vaccine.

Endometriosis is widely perceived as an estrogen-dependent chronic disorder with infertility and pelvic pain. Although the etiology of endometriosis has remained elusive, many studies have proclaimed the relevance of immune system disorders with endometriosis. With the discovery that the dysregulation of multiple biological functions in endometriosis is caused by the aberrant differentiation of T helper cells, a shift towards Th2 immune response may account for the disease progression. This review attempts to present mechanisms of cytokines, chemokines, signal pathways, transcription factors and some other factors related with the derivation of Th1/Th2 immune response involved in the development of endometriosis. The current understanding of treatment approaches and potential therapeutic targets will also be outlined with brief discussion.

Endometriosis (EMS) is a challenging gynecological disorder prevalent in reproductive-aged women, and Th1/Th2 cytokines are implicated in EMS progression. This study probed the serum levels and clinical values of Th1/Th2 cytokines in EMS patients. Firstly, the clinic characteristics of EMS and control patients were recorded. The levels of interferon (IFN)-γ, interleukin (IL)-2, IL-4, and IL-10 in the serum of EMS and control patients were identified, respectively. The correlations between Th1 and Th2 cytokines and the diagnostic values of these cytokines in EMS were analyzed. We observed that EMS patients had obvious differences from the controls in dysmenorrhea, dyspareunia, pelvic pain, nulliparous, and CA125 levels. Serum IFN-γ and IL-2 were lower while IL-4 and IL-10 were higher in EMS patients. Serum IFN-γ, IL-4 were negatively correlated with serum IL-2, and IL-10 in EMS patients. Th1/Th2 cytokines may help the diagnosis of EMS. Serum IFN-γ and IL-2 were independent protective factors for EMS while dysmenorrhea, dyspareunia, nulliparous, and serum IL-4 and IL-10 were independent risk factors for EMS. Collectively, serum Th1/Th2 cytokine levels helped the diagnosis of EMS, with IFN-γ and IL-2 serving as independent protective factors whilst IL-4 and IL-10 serving as independent risk factors.

Is interleukin-10 (IL-10) anti-fibrotic in endometriosis?

IL-10 is not anti-fibrotic but pro-fibrotic in endometriosis, because IL-10 treatment of endometriotic stromal cells in vitro promotes myofibroblast proliferation and collagen type I protein expression.

We previously showed that persistent activation of signal transducer and activator of transcription 3 (STAT3) via IL-6 trans-signaling promotes fibrosis of endometriosis. Studies showed marked anti-fibrotic effects of IL-10 via the STAT3 signaling pathway, which is generally considered to be anti-inflammatory, in various organs.

Endometrial and/or endometriotic samples of 54 patients who had histological evidence of deep endometriosis, and endometrial samples from 30 healthy fertile women were analyzed.

The effects of IL-10/STAT3 signaling as well as inhibition of STAT3 activation by knockdown of STAT3 gene on the pro-fibrotic phenotype in endometrial and endometriotic stromal cells in vitro were investigated. Then, the effects of various time points of IL-10 treatment in combination with transforming growth factor (TGF)-β1 and/or IL-6/soluble IL-6 receptor (sIL-6R) on the profibrotic phenotype of endometrial and endometriotic stromal cells were investigated.

IL-10 induced pro-fibrotic phenotype (cell proliferation, collagen type I synthesis, α-smooth muscle actin positive stress fibers and collagen gel contraction) of endometriotic stromal cells. Knockdown of STAT3 gene decreased the IL-10 induced pro-fibrotic phenotype of endometriotic stromal cells. In contrast, IL-10 had no significant effects on pro-fibrotic phenotype of endometrial stromal cells of healthy women. Sequential IL-10 treatment with or without TGF-β1 and/or IL-6/sIL-6R induced persistent activation of STAT3 and significantly increased proliferation of myofibroblasts (cells with α-smooth muscle actin positive stress fibers) and protein expression of collagen type I in endometriotic stromal cells. TGF-β1 and/or IL-6/sIL6RIL-6/sIL6R treatment significantly increased tissue inhibitor of metalloproteinase 1 (TIMP1) protein expression, whereas IL-10 had no significant effects. Knockdown of STAT3 gene significantly decreased the TGF-β1 and/or IL-6/sIL6R induced TIMP1 protein expression. In contrast, pre-treatment with IL-10 before TGF-β1 and/or IL-6/sIL-6R treatment and sequential IL-10 treatment with or without TGF-β1 and/or IL-6/sIL-6R significantly decreased proliferation of fibroblasts (cells without α-smooth muscle actin positive stress fibers) and collagen type I protein expression in endometrial stromal cells of healthy women.

N/A.

Given the large number of complex interactions and signaling pathways of pro- and anti-inflammatory mediators that are involved in the pathophysiology of endometriosis, the present study investigated only a very small portion of the whole. Further in vivo studies are required to validate the present findings.

Inflammatory mediators in the pathophysiology of endometriosis have been extensively investigated as potential therapeutic targets. However, the present study showed that anti-inflammatory signals of IL-10 and IL-6 through persistent STAT3 activation may promote endometriosis fibrosis. Therapeutic strategies, such as suppression of 'inflammation', might dysregulate the cross-regulation of 'pro- and anti-inflammatory mediators', leading to detrimental effects in patients with endometriosis, such as fibrosis. To develop new, but not deleterious, therapeutic strategies, studies are required to investigate whether, how and what 'anti-inflammatory mediators' along with pro-inflammatory mediators are involved in individual patients with endometriosis.

This study was supported in part by KARL STORZ SE & Co. KG (Tuttlingen, Germany). The authors have no conflict of interest to disclose.

Endometriosis is a hormone-dependent inflammatory disease characterized by the existence of endometrial tissues outside the uterine cavity. Pharmacotherapy and surgery are the current dominant management options for endometriosis. The greater incidence of recurrence and reoperation after surgical treatment as well as the adverse effects of medical approaches predispose patients to potential limitations for their long-term usage. Consequently, it is essential to explore novel supplementary and alternative drugs to ameliorate the therapeutic outcomes of endometriotic patients. Resveratrol is a phenolic compound that has attracted increasing interest from many researchers due to its pleiotropic biological activities. Here, we review the possible therapeutic efficacies and molecular mechanisms of resveratrol against endometriosis based on in vitro, animal, and clinical studies. The potential mechanisms of resveratrol include anti-proliferative, pro-apoptotic, anti-angiogenic, anti-oxidative stress, anti-invasive and anti-adhesive effects, thereby suggesting that resveratrol is a promising candidate for endometriosis. Because most studies have investigated the effectiveness of resveratrol on endometriosis via in vitro trials and/or experimental animal models, further high-quality clinical trials should be undertaken to comprehensively estimate the clinical application feasibility of resveratrol on endometriosis.

Some patients with advanced clear-cell ovarian cancer (CCOC) respond to immunotherapy; however, little is known about the tumor microenvironment (TME) of this relatively rare disease. Here, we describe a comprehensive quantitative and topographical analysis of biopsies from 45 patients, 9 with Federation Internationale des Gynaecologistes et Obstetristes (FIGO) stage I/II (early CCOC) and 36 with FIGO stage III/IV (advanced CCOC). We investigated 14 immune cell phenotype markers, PD-1 and ligands, and collagen structure and texture. We interrogated a microarray data set from a second cohort of 29 patients and compared the TMEs of ARID1A-wildtype (ARID1Awt) versus ARID1A-mutant (ARID1Amut) disease. We found significant variations in immune cell frequency and phenotype, checkpoint expression, and collagen matrix between the malignant cell area (MCA), leading edge (LE), and stroma. The MCA had the largest population of CD138+ plasma cells, the LE had more CD20+ B cells and T cells, whereas the stroma had more mast cells and αSMA+ fibroblasts. PD-L2 was expressed predominantly on malignant cells and was the dominant PD-1 ligand. Compared with early CCOC, advanced-stage disease had significantly more fibroblasts and a more complex collagen matrix, with microarray analysis indicating "TGFβ remodeling of the extracellular matrix" as the most significantly enriched pathway. Data showed significant differences in immune cell populations, collagen matrix, and cytokine expression between ARID1Awt and ARID1Amut CCOC, which may reflect different paths of tumorigenesis and the relationship to endometriosis. Increased infiltration of CD8+ T cells within the MCA and CD4+ T cells at the LE and stroma significantly associated with decreased overall survival.

Endometriosis is a common gynecological disorder seen in women and is characterized by chronic pelvic pain and infertility. This disorder is becoming more prevalent with increased morbidity. The etiology of endometriosis remains to be fully elucidated, which will lead to improved therapeutic options. In this review, we will evaluate the biochemical mechanisms leading to oxidative stress and their implication in the pathophysiology of endometriosis, as well as potential treatments that target these processes. A comprehensive exploration of previous research revealed that endometriosis is associated with elevated reactive oxygen species and oxidation products, decreased antioxidants and detoxification enzymes, and dysregulated iron metabolism. High levels of oxidative stress contributed to inflammation, extracellular matrix degradation, angiogenesis, and cell proliferation, which may explain its role in endometriosis. Endometriosis-associated pain was attributed to neurogenic inflammation and a feed-forward mechanism involving macrophages, pro-inflammatory cytokines, and pain-inducing prostaglandins. N-acetylcysteine, curcumin, melatonin, and combined vitamin C and E supplementation displayed promising results for the treatment of endometriosis, but further research is needed for their use in this population.

Appropriate decidualization is of great importance for embryo implantation, placental development and successful pregnancy. Although it has been well-acknowledged that decidualization relies on activation of progesterone-mediated signaling pathway, the exact mechanisms have not been elucidated. Here, we demonstrated that both IL-27 and IL27RA were highly expressed in decidua than those in endometrium during secretory phase. Estrogen plus progesterone significantly upregulated the expression of IL-27 and IL-27RA in endometrium stromal cells (ESCs). In addition, inhibiting IL-27 signaling with IL-27 neutralization antibody (anti-IL-27) suppressed the expression of decidualization-related molecules, receptors of estrogen (gene coded by ESR) and progesterone (PGR) induced by cAMP or estrogen plus progesterone. Similar results were obtained from Il27ra-/- (knockout of Il27ra) female mice. Moreover, knockout of Il27ra did not affect the estrus cycle and folliculogenesis in mice but reduced implantation rate with the impairing decidualization. Mechanistically, IL-27 upregulated the expression of ESR1, ESR2 and PGR in ESCs and DSCs, as well as the phosphorylation level of STAT3. In the presence of estrogen plus progesterone, treatment with ESCs with anti-IL-27 inhibited the activation of STAT3. Also, the expression of ESR, PGR was decreased in Il27ra-/- mice. In conclusion, these findings demonstrate that IL-27 upregulated by estrogen and progestogen promotes decidualization possibly through a STAT3-dominant pathway.

Endometriosis is a chronic inflammatory disease associated with the growth and proliferation of endometrial-like tissues outside the uterus. Although the exact etiology and mechanism of the pathogenesis of the disease have not been fully elucidated, the immune system cells and the mediators produced by them can be named as effective factors in the onset and progression of the disease.

We aim to attempt to review studies on the role of the immune system in endometriosis to better understand the pathogenesis of endometriosis.

Abundant production of inflammatory mediators by neutrophils and macrophages and reduced cytotoxicity of defined cells promote endometriosis at the early stages of the disease. Following an increase in the inflammation of the environment, the body takes compensatory mechanisms to reduce inflammation and establish homeostasis. For this purpose, the body produces remodeling and anti-inflammatory factors leading to slow conversion of the inflammatory environment into a non-inflammatory environment with proliferative and immunosuppressive properties. Environmental conditions induce M2 macrophages, TH2 cells, and Tregs differentiation, promoting disease progression by producing angiogenic and immunosuppressive factors. However, the exact molecular mechanism involved in changing inflammatory to non-inflammatory conditions is not yet fully understood.

Due to the common characteristics of endometriotic cells and cancer cells, most potential treatment options for endometriosis have been suggested due to the results of these methods in the treatment of cancer. In this pathway, immune system cells and soluble mediators can be used as targets.

Endometriosis is a condition that is influenced by hormones and involves stroma and glands being found outside the uterus; there are increases in proliferation, invasion, internal bleeding, and fibrosis. Matrix metalloproteinases (MMPs) have been suggested to be crucial in the progression of invasion. The MMP family includes calcium-dependent zinc-containing endopeptidases, some of which not only affect the process of cell invasion but also participate in other physiological and pathological processes, such as angiogenesis and fibrosis. MMPs act as downstream-targeted molecules and their expression can be regulated by numerous factors such as estrogen, oxidative stress, cytokines, and environmental contaminants. Given their unique roles in endometriosis, MMPs may become effective biomarkers of endometriosis in the future. In the present review, we summarize the current literature on MMPs regarding their classification, function, and potential value for endometriosis, which may contribute to our knowledge of MMPs and MMP-targeted interventions.

Endometriosis is a female reproductive disorder characterized by growth of uterine cells and tissue in distant sites. Around 2-10% of women experience this condition during reproductive age, 35-50% of whom encounter fertility issues or pain. To date, there are no established methods for its early diagnosis and treatment, other than surgical procedures and scans. It is difficult to identify the disease at its onset, unless symptoms such as infertility and/or pain are present. Determining the mechanisms involved in its pathogenesis is vital, not only to pave the way for early identification, but also for disease management and development of less invasive but successful treatment strategies. Endometriosis is characterized by cell proliferation, propagation, evasion of immunosurveillance, and invasive metastasis. This review reports the underlying mechanisms that are individually or collectively responsible for disease establishment and evolution. Treatment of endometriosis mainly involves hormone therapies, which may be undesirable or have their own repercussions. It is therefore important to devise alternative strategies that are both effective and cause fewer side effects. Use of phytochemicals may be one of them. This review focuses on pharmacological inhibitors that can be therapeutically investigated in terms of their effects on signaling pathways and/or mechanisms involved in the pathogenesis of endometriosis.

Endometriosis is a gynecological non-malignant disease that is manifested by the presence of extrauterine ectopic endometrial cells and stroma. The aim of current study was to explore the role of tumor necrosis factor receptor type 1-associated death domain (TRADD) protein in endometriosis.

Cell migration, invasion, and the expression of epithelial-mesenchymal transition (EMT) inducers in TRADD silencing or overexpression in eutopic endometrial stromal cells (EuSCs) and ectopic endometrial stromal cells (EcSCs) were analyzed by wound healing assay, transwell assay, quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting and rat endometriosis model. A cell line derived from THP-1 macrophages was used to measure M1/M2 polarization in endometriosis by flow cytometry and enzyme-linked immunosorbent assay (ELISA).

The mRNA level and protein expression of TRADD, keratin, E-cadherin, N-cadherin, vascular endothelial growth factor, matrix metalloproteinase-9, CD40, and CD206 were abnormally expressed in ectopic endometrial tissues and EcSCs. TRADD silencing promoted migration, invasion, and EMT in EuSCs, while TRADD overexpression restrained migration, invasion, and EMT in EcSCs. TRADD knockdown prohibited M1/M2 polarization in normal endometrial homogenization-treated THP-1-derived macrophages, whereas TRADD upregulation facilitated M1/M2 polarization in patients with endometrial homogenization-treated THP-1-derived macrophages. In addition, TRADD overexpression suppressed ectopic endometrial cysts formation in a rat endometriosis model. TRADD overexpression activated NF-κB and MAPK signaling in EcSCs and rat models.

Our results indicated that the overexpression of TRADD prohibited migration, invasion, EMT, M1/M2 polarization and ectopic endometrial cysts formation in endometriosis, and this might due to regulating NF-κB and MAPK signaling.