Development Of Endometriosis Research Articles

Bioinformatic Analysis of m6A Regulator-Mediated RNA Methylation Modification Patterns and Immune Microenvironment Characterization in Endometriosis.

Epigenetic regulation plays an essential role in immunity and inflammation in endometriosis. In this study, we aimed to explore differences in m6A regulators between endometriosis patients and normal women and analyze the effect of m6A modification on immune and inflammatory microenvironment. The samples for analysis were downloaded from the Gene Expression Omnibus database, including ectopic endometrium (EC), eutopic endometrium (EU), and normal eutopic endometrium (NM) samples from non-endometriosis women. The validation process involved utilizing our previous RNA-sequencing data. Subsequently, a correlation analysis was performed to ascertain the relationship between m6A and the inflammatory microenvironment profile, encompassing infiltrating immunocytes, immune-inflammation reaction gene sets, and human leukocyte antigen genes. LASSO analyses were used to develop risk signature. The findings of this study indicate that the m6A regulators FTO were observed to be significantly up-regulated, while YTHDF2, CBLL1, and METTL3 were down-regulated in endometriosis tissues. The CIBERSORT analysis revealed that the local inflammatory microenvironment of ectopic lesions plays a crucial role in the development of endometriosis. Notably, M2 macrophages exhibited a significant difference between the EC and NM groups. Moreover, M2 macrophages demonstrated a positive correlation with FTO (0.39) and a negative correlation with CBLL1 (-0.35). Furthermore, consistent clustering of EC and EU samples resulted in the identification of three distinct cell subtypes. Among different cell subtypes, significant differences were in immunoinfiltrating cells, plasma cells, naive CD4 T cells, memory activated CD4 T cells, gamma delta T cells, resting NK cells and activated NK cells but not in macrophages. Furthermore, the identification of various compounds capable of targeting these m6A genes was achieved. In conclusions, our integrated bioinformatics analysis results demonstrated that m6A-related genes METTL3, CBLL1 and YTHDF2 may be useful biomarkers for endometriosis in ectopic endometrium. The potential therapeutic approach of targeting m6A regulators holds promise for the treatment of endometriosis.

Changes of serum CA125 and PGE2 before and after high-intensity focused ultrasound combined with GnRH-a in treatment of patients with adenomyosis.

This study aimed to investigate the changes of serum carbohydrate antigen 125 (CA125) and prostaglandin E2 (PGE2) in patients with adenomyosis before and after treatment with high-intensity focused ultrasound (HIFU) combined with gonadotropin-releasing hormone agonist (GnRH-a). One hundred and sixty-five patients with adenomyosis who received HIFU combined with GnRH-a were selected as case group. Sixty-five healthy women who underwent physical examination at the same time were taken as normal control group. At the end of follow-up 6 months after treatment, the case group were divided into effective subgroup and ineffective subgroup according to clinical efficacy. Changes of serum CA125 and PGE2 were analyzed. Serum CA125 and PGE2 levels in the case group were higher than those in the normal control group before treatment (both P < 0.001). Serum CA125 and PGE2 levels in the case group 6 months after treatment were lower than those before treatment (both P < 0.001). There was no difference in serum CA125 and PGE2 levels between effective subgroup and ineffective subgroup before treatment (P = 0.351, 0.284, respectively). Serum CA125 and PGE2 levels in the effective subgroup were lower than those in the ineffective subgroup 6 months after treatment (both P < 0.001). Serum CA125 and PGE2 may be involved in the development of adenomyosis, and their expression levels may be related to the prognosis of patients. Levels of serum CA125 and PGE2 in patients with adenomyosis decrease after treatment with HIFU combined with GnRH-a. The detection of serum CA125 and PGE2 may be used as an index to diagnose adenomyosis and evaluate the therapeutic effect of HIFU combined with GnRH-a.

Role of the gut microbiota in the pathogenesis of endometriosis: a review.

Endometriosis is classically defined as a chronic inflammatory heterogeneous disorder occurring in any part of the body, characterized by estrogen-driven periodic bleeding, proliferation, and fibrosis of ectopic endometrial glands and stroma outside the uterus. Endometriosis can take overwhelmingly serious damage to the structure and function of multi-organ, even impair whole-body systems, resulting in severe dysmenorrhea, chronic pelvic pain, infertility, fatigue and depression in 5-10% women of reproductive age. Precisely because of a huge deficiency of cognition about underlying etiology and complex pathogenesis of the debilitating disease, early diagnosis and treatment modalities with relatively minor side effects become bottlenecks in endometriosis. Thus, endometriosis warrants deeper exploration and expanded investigation in pathogenesis. The gut microbiota plays a significant role in chronic diseases in humans by acting as an important participant and regulator in the metabolism and immunity of the body. Increasingly, studies have shown that the gut microbiota is closely related to inflammation, estrogen metabolism, and immunity resulting in the development and progression of endometriosis. In this review, we discuss the diverse mechanisms of endometriosis closely related to the gut microbiota in order to provide new approaches for deeper exploration and expanded investigation for endometriosis on prevention, early diagnosis and treatment.

Novel Diagnostic Biomarker BST2 Identified by Integrated Transcriptomics Promotes the Development of Endometriosis via the TNF-α/NF-κB Signaling Pathway.

Endometriosis (EMS) is a common gynecological condition with apparent heterogeneity, lack of diagnostic markers, and unclear pathogenesis. A series of bioinformatics methods were employed to explore EMS's pathological mechanisms and potential biomarkers by analyzing the combined datasets of EMS (GSE7305, GSE7307, GSE58198, E-MTAB-694), which included 34 normal, 127 eutopic, and 46 ectopic endometrium samples. Then, wet-laboratory experiments (including Western blot, qRT-PCR, and Immunohistochemistry, Immunofluorescence, CCK-8, EdU, Wound healing, Transwell, and Adhesion assays) were applied to examine the biomarkers' expression and function in primary endometrial stromal cells. Bioinformatic analysis indicated that the core pathogenesis of EMS was dysregulated immune-inflammation and tissue remolding processes. Among the upregulated DEGs, BST2 was screened as a potential diagnostic biomarker in EMS, which associated with the revised American Fertility Society (r-AFS) stage and immune-inflammation processes of EMS. Moreover, BST2's overexpression was affirmed in the RNA and protein levels in EMS tissues. In vitro experiments demonstrated that TNF-α promoted the expression of BST2 in ESCs. And BST2 knockdown inhibited migration, invasion, adhesion, and inflammation except for the proliferation of ESCs, probably via the TNF-α/NF-κB pathway. Through a combination of wet and dry studies, we concluded that the core pathogenesis of endometriosis was dysregulated immune-inflammation and tissue remolding, and BST2 might be a potential diagnostic and therapeutic target in endometriosis.

Pyroptotic T cell-derived active IL-16 has a driving function in ovarian endometriosis development

Endometriosis, affecting 6%-10% of women, often leads to pain and infertility and its underlying inflammatory mechanisms are poorly understood. We established endometriosis models in wild-type and IL16KO mice, revealing the driver function of IL-16 in initiating endometriosis-related inflammation. Using an invitro system, we confirmed iron overload-induced GSDME-mediated pyroptosis as a key trigger for IL-16 activation and release. In addition, our research led to the development of Z30702029, a compound inhibiting GSDME-NTD-mediated pyroptosis, which shows promise as a therapeutic intervention for endometriosis. Importantly, our findings extend beyond endometriosis, highlighting GSDME-mediated pyroptosis as a broader pathway for IL-16 release and offering insights into potential treatments for various inflammatory conditions.

Focusing on the role of protein kinase mTOR in endometrial physiology and pathology: insights for therapeutic interventions.

The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase crucial for cellular differentiation, proliferation, and autophagy. It shows a complex role in the endometrium, influencing both normal and pathogenic conditions. mTOR promotes the growth and maturation of endometrial cells, enhancing endometrial receptivity and decidualization. However, it also contributes to the development of endometriosis (EMs) and endometrial cancer (EC), thus emerging as a therapeutic target for these conditions. In this review, we summarize recent research progress on the mTOR signalling pathway in the endometrium. This provides insights into female endometrial structure and function and guides the prevention and treatment of related diseases.

Extracellular vesicle-encapsulated miR-25-3p promotes epithelial-mesenchymal transition and migration of endometrial epithelial cells by inducing macrophage polarization.

The pathogenesis of adenomyosis is closely related to the epithelial-mesenchymal transition and macrophages. MicroRNAs have been extensively investigated in relation to the epithelial-mesenchymal transition in a range of malignancies. However, there is a paucity of research on extracellular vesicles derived from the eutopic endometrium of adenomyosis and their encapsulated microRNAs. In this study, we investigated the role of microRNA-25-3p derived from extracellular vesicles in inducing macrophage polarization and promoting the epithelial-mesenchymal transition in endometrial epithelial cells of patients with adenomyosis and controls. We obtained eutopic endometrial samples and isolated extracellular vesicles from the culture supernatant of primary endometrial cells. Real-time quantitative PCR analysis demonstrated that microRNA-25-3p was highly expressed in extracellular vesicles, as well as in macrophages stimulated by extracellular vesicles from eutopic endometrium of adenomyosis; and macrophages transfected with microRNA-25-3p exhibited elevated levels of M2 markers, while displaying reduced levels of M1 markers. After co-culture with the above polarized macrophages, endometrial epithelial cells expressed higher levels of N-cadherin and Vimentin, and lower protein levels of E-cadherin and Cytokeratin 7. It was revealed that microRNA-25-3p encapsulated in extracellular vesicles from eutopic endometrial cells could induce macrophage polarization toward M2, and the polarized macrophages promote epithelial-mesenchymal transition in epithelial cells. However, in vitro experiments revealed no significant disparity in the migratory capacity of endometrial epithelial cells between the adenomyosis group and the control group. Furthermore, it was observed that microRNA-25-3p-stimulated polarized macrophages also facilitated the epithelial-mesenchymal transition and migration of endometrial epithelial cells within the control group. Thus, the significance of microRNA-25-3p-induced polarized macrophages in promoting the development of adenomyosis is unclear, and macrophage infiltration alone may be adequate for this process. We emphasize the specificity of the local eutopic endometrial microenvironment and postulate its potential significance in the pathogenesis of adenomyosis.

HIF-1α regulates DcR3 to promote the development of endometriosis

ObjectiveThe aim of this study was to investigate the expression and clinical significance of HIF-1α and DcR3 in endometriosis by analysing clinical case data. Tissue samples were collected for tissue chip analysis and staining, and human endometrial stromal cells were isolated and cultured for cell experiments. Additionally, experiments were conducted on collected peritoneal fluid to explore the association and role of HIF-1α and DcR3 in endometriosis. Study DesignPatients who visited the Department of Obstetrics and Gynaecology at Central Hospital in Fengxian District, Shanghai, from January 2018 to December 2021 were recruited for this controlled study. Clinical data and tissue chip staining results were collected for multiple regression analysis on the clinical significance of HIF-1α and DcR3. Endometrial tissue, ovarian cysts, and pelvic fluid were collected, and human endometrial stromal cells were cultured. The impact of HIF-1α on DcR3 in different oxygen environments and its role in endometriosis were investigated through PCR, Western blotting, enzyme-linked immunosorbent assay, as well as adhesion and migration assays. ResultsIn patients with endometriosis, the expression of DcR3 and HIF-1α was found to be upregulated and correlated in ectopic endometrium. The expression of DcR3 served as an indicator of the severity of endometriosis. Hypoxia induced the expression of DcR3, which was regulated by HIF-1α and promoted migration and adhesion. ConclusionDcR3 can be used as a clinical indicator to assess the severity of endometriosis. The hypoxic environment in endometriosis enhances disease progression by regulating DcR3 through HIF-1α.

Research Progress of Caspase in Endometriosis.

Endometriosis, a common chronic gynecological disease, refers to the presence and proliferation of endometrial tissue in locations other than the uterine cavity. Approximately 6 to 10% of the population of women of childbearing age are known to have endometriosis; the most common clinical signs are pelvic pain and infertility. Although endometriosis is a benign disease, it exhibits some typical features of malignant tumors, such as proliferation, invasion, metastasis, and recurrence. Endometriosis is considered a chronic, inflammatory, and estrogen-dependent disease, and multiple factors contribute to its occurrence and development. In recent years, increasing attention has been given to the role of apoptosis in the pathogenesis of this disease. Some researchers believe that spontaneous apoptosis of the endometrium is critical in maintaining its normal structure and function, and abnormal apoptosis can promote the occurrence and development of endometriosis. Inflammation is another likely process in the pathogenesis of endometriosis. Inflammation mediates the adhesion, proliferation, differentiation, and invasion of ectopic lesions of endometriosis, primarily by regulating the function of immune cells and increasing the level of proinflammatory cytokines in body fluids. The ultimate initiators of apoptosis and inflammatory cell death (pyroptosis) are the caspase family proteases. In this article, we review the progress in recent years in caspase function as well as the possible role of these enzymes in the pathogenesis of endometriosis, indicating potential treatment strategies.

AURKA Enhances the Glycolysis and Development of Ovarian Endometriosis Through ERβ.

Ovarian endometriosis (EMs) is a benign, estrogen-dependent gynecological disorder. Estrogen receptor beta (ERβ), a nuclear receptor for estradiol, plays an important role in the development of ovarian EMs. Here, we investigated the biological significance of aurora kinase A (AURKA) in ovarian EMs and the mechanism by which it regulates ERβ. We used immunohistochemical assays to verify that AURKA and ERβ were highly expressed in ectopic endometrial tissues. Cell proliferation and colony formation assays were used to demonstrate that AURKA promoted the proliferation of EMs cells. Wound-healing assay, Transwell migration assay, and Matrigel invasion assay further showed that AURKA enhanced the ability of EMs cells to migrate and invade. In addition, AURKA was shown to stimulate glycolysis in EMs cells by measuring the concentration of glucose and lactate in the cell supernatants. Moreover, the AURKA inhibitor alisertib was found to inhibit the progression of ovarian EMs and glycolysis in a mouse model of EMs by measuring ectopic tissues as well as by testing the peritoneal fluid of mice. Furthermore, coimmunoprecipitation assay showed that AURKA interacted with ERβ. The rescue experiments confirmed that AURKA regulated the development and glycolysis of ovarian EMs in an ERβ-dependent manner. AURKA contributed to the development of ovarian EMs by upregulating of ERβ. AURKA may represent a new target for the treatment of ovarian EMs.

Dysmenorrhea pattern in adolescences informing adult endometriosis

BackgroundEndometriosis (EMs) is a chronic and progressive disease that, if diagnosed late, can lead to infertility and deep infiltrating endometriosis (DIE). Dysmenorrhea is the most prominent symptom of EMs. However, limited research exists on the specific correlation between dysmenorrhea patterns and EMs. Early prevention of EMs is essential to effectively manage the progression of the disease, and is best detected during adolescence. Our objective was to associate the development of EMs with dysmenorrhea patterns during adolescence and quantify the risk of adult EMs for adolescent girls, with the aim of supporting primary intervention strategy planning.MethodsThis case–control study examined predictors for adult EMs based on dysmenorrhea patterns in adolescents. We collected 1,287 cases of 641 EMs and 646 healthy females regarding their basic demographic information, adolescent menstrual characteristics, adolescent dysmenorrheal patterns, and adolescent lifestyles. Age-matching (1-to-1) was employed to control for the confounding effect of age between the groups. Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression models were utilized to identify predictors for adult EMs. The predictive value of the model was evaluated using the area under the receiver operating characteristic curve (AUC) and the C-index, while Hosmer–Lemeshow Test assessed the goodness of fit of the model. Data from one additional cohort in Shenzhen hospitalized with EMs were used to external validation were analyzed.ResultsIndividuals who always experienced dysmenorrhea had a risk of adult endometriosis 18.874 (OR = 18.874; 95%CI = 10.309–34.555) times higher than those occasional dysmenorrhea, The risk of developing EMs was 5.257 times higher in those who experienced dysmenorrhea more than 12 months after menarche than in those who experienced dysmenorrhea less than 6 months after menarche (OR = 5.257, 95% CI = 3.343–8.266), AUC in the external validation cohort was 0.794(95%CI: 0.741–0.847). We further found that high-intensity physical activity and sun-sensitive skin of burning were influential factors in high-frequency dysmenorrhea. The AUC value for the internal evaluation of the model was 0.812 and the AUC value for the external validation was 0.794.ConclusionOur findings revealed that the frequency of dysmenorrhea during adolescence contributed to the development of adult endometriosis. The frequency and onset of dysmenorrhea in adolescence were promising predictors for adult EMs. Both internal and external validation proved the model's good predictive ability.Trial registrationhttp://www.chictr.org.cn/, TRN: ChicTR2200060429, date of registration: 2022/06/01, retrospectively registered.

Role of TGF-Beta in the progression and development of endometriosis

Role of TGF-Beta in the progression and development of endometriosis

The roles of chromatin regulatory factors in endometriosis.

Endometriosis is an estrogen-dependent inflammatory disease and one of the most common gynecological diseases in women of reproductive age. The aim of the review was to explore the relationship between the chromatin regulatory factors and endometriosis. By searching for literature on chromatin regulators and endometriosis in PuMed. Finally, 98 documents were selected. Chromatin regulators (CRs) are essential epigenetic regulatory factors that can regulate chromatin structure changes and are usually divided into three categories: DNA methylation compounds, histone modification compounds, and chromatin remodeling complexes. Noncoding RNAs are also chromatin regulators and can form heterochromatin by binding to protein complexes. Chromatin regulators cause abnormal gene expression by regulating chromatin structure, thereby affecting the occurrence and development of endometriosis. This review summarizes the participation of chromatin regulators in the mechanisms of endometriosis, and these changes in related chromatin regulators provide a comprehensive reference for diagnosis and treatment of endometriosis.

The Impact of Endometriosis on Pregnancy.

Despite the increased frequency of endometriosis, it remains one of the most enigmatic disorders regarding its effects on pregnancy. Endometriosis adversely affects both natural and assisted conception. Impaired folliculogenesis, which causes follicular dysfunction and low egg quality, as well as luteal phase problems, reduced fertilization, and abnormal embryogenesis, are some of the mechanisms advocated to explain reproductive dysfunction. There is a rising need for a comprehensive study of the potential negative consequences of this condition on pregnancy outcomes, including the postpartum period, as more women with a medical history of endometriosis become pregnant. Obstetrical complications (small for gestational age [SGA], cesarean section [CS], miscarriage, hemorrhage, low placental adhesion, and preterm delivery) are statistically elevated in women with endometriosis. Furthermore, ruptured ovarian endometrioma, appendicitis, intestinal perforation, and hemoperitoneum have been described in pregnancy. Obstetricians are largely unfamiliar with these complications, as they have not been thoroughly investigated. The development and pathogenesis of endometriosis is an important field of study and has not yet been fully elucidated. Finding these mechanisms is crucial for the development of new and more effective strategies to treat this condition. Endometriosis can have an impact on obstetric and neonatal outcomes of pregnancy, in addition to its potential effects on conception. To date, no additional monitoring is recommended for pregnancies with a history of endometriosis. However, more studies are urgently needed to assess the need for the tailored pregnancy monitoring of women with endometriosis.

ERβ-activated LINC01018 promotes endometriosis development by regulating the CDC25C/CDK1/CyclinB1 pathway

Endometriosis refers to as an estrogen-dependent disease. Estrogen receptor β (ERβ), the main estrogen receptor subtype which is encoded by the estrogen receptor 2 (ESR2) gene, can mediate the action of estrogen in endometriosis. Although selective estrogen receptor modulators can target the ERβ, they are not specific due to the wide distribution of ERβ. Recently, long noncoding RNAs have been implicated in endometriosis. Therefore, we aim to explore and validate the downstream regulatory mechanism of ERβ, and to investigate the potential role of long intergenic noncoding RNA 1018 (LINC01018) as a nonhormonal treatment for endometriosis. Our study demonstrates that the expression levels of ESR2 and LINC01018 are increased in ectopic endometrial tissues and reveals a significant positive correlation between the ESR2 and LINC01018 expression. Mechanistically, ERβ directly binds to an estrogen response element located in the LINC01018 promoter region and activates LINC01018 transcription. Functionally, ERβ can regulate the CDC25C/CDK1/CyclinB1 pathway and promote ectopic endometrial stromal cell proliferation via LINC01018 in vitro. Consistent with these findings, the knockdown of LINC01018 inhibits endometriotic lesion proliferation in vivo. In summary, our study demonstrates that the ERβ/LINC01018/CDC25C/CDK1/CyclinB1 signaling axis regulates endometriosis progression.

How Can Selected Dietary Ingredients Influence the Development and Progression of Endometriosis?

Endometriosis is a chronic, hormone-dependent disease characterized by the presence of endometrial tissue in ectopic locations. Since the treatment options for this disease are still limited, and the cure rate is unsatisfactory, the search for ways to treat symptoms and modify the course of the disease is of key importance in improving the quality of life of patients with endometriosis. So far, the literature has shown that nutrition can influence endometriosis through hormonal modification and altering the inflammatory or oxidative response. Since the importance of nutrition in this disease is still a subject of scientific research, we aimed to summarize the current knowledge on the role of dietary modifications in endometriosis. Our review showed that nutrients with anti-inflammatory and antioxidant properties, including most vitamins and several trace elements, may influence the pathogenesis of endometriosis and can be considered as the nutrients preventing the development of endometriosis. However, despite the many discoveries described in this review, further interdisciplinary research on this topic seems to be extremely important, as in the future, it may result in the development of personalized therapies supporting the treatment of endometriosis.

Evodiamine suppresses endometriosis development induced by early EBV exposure through inhibition of ERβ.

Introduction: Endometriosis (EMS) is characterized as a prevalent gynecological inflammatory disorder marked by the existence of endometrial tissues situated beyond the uterus. This condition leads to persistent pelvic pain and may contribute to infertility. In this investigation, we explored the potential mechanism underlying the development of endometriosis (EMS) triggered by transient exposure to either latent membrane protein 1 (LMP1) or Epstein-Barr virus (EBV) in a mouse model. Additionally, we examined the potential inhibitory effect of evodiamine (EDM) on EMS. Methods: Immortalized human endometrial stromal cells (HESC) or epithelial cells (HEEC) were transiently exposed to either EBV or LMP1. The presence of evodiamine (EDM) was assessed for its impact on estrogen receptor β (ERβ) expression, as well as on cell metabolism parameters such as redox balance, mitochondrial function, inflammation, and proliferation. Additionally, a mixture of LMP1-treated HESC and HEEC was administered intraperitoneally to generate an EMS mouse model. Different dosages of EDM were employed for treatment to evaluate its potential suppressive effect on EMS development. Results: Transient exposure to either EBV or LMP1 triggers persistent ERβ expression through epigenetic modifications, subsequently modulating related cell metabolism for EMS development. Furthermore, 4.0µM of EDM can efficiently reverse this effect in in vitro cell culture studies. Additionally, 20mg/kg body weight of EDM treatment can partly suppress EMS development in the in vivo EMS mouse model. Conclusion: Transient EBV/LMP1 exposure triggers permanent ERβ expression, favoring later EMS development, EDM inhibits EMS development through ERβ suppression. This presents a novel mechanism for the development of endometriosis (EMS) in adulthood stemming from early Epstein-Barr virus (EBV) exposure during childhood. Moreover, evodiamine (EDM) stands out as a prospective candidate for treating EMS.

Unraveling the relationship between gut microbiota and site-specific endometriosis: a Mendelian randomization analysis.

Although numerous studies have illustrated the connection between gut microbiota and endometriosis, a conspicuous gap exists in research focusing on the pathogenesis of endometriosis at various sites and its linkage with infertility. In this study, we used a two-sample Mendelian randomization analysis to investigate the effect of gut microbiota on the development of endometriosis in different regions, including the uterus, ovary, fallopian tube, pelvic peritoneum, vagina, and rectovaginal septum, as well as the intestine. Additionally, we explored the correlation between gut microbiota and endometriosis-induced infertility. Genetic associations with gut microbes were obtained from genome-wide association study (GWAS) datasets provided by the MiBioGen consortium, whereas endometriosis-related GWAS data were sourced from the FinnGen dataset. In our analysis, single-nucleotide polymorphisms were used as instrumental variables, with the primary estimation of the causal effect performed via the inverse variance weighting method. Our sensitivity analyses incorporated heterogeneity tests, pleiotropy tests, and the leave-one-out method. We identified associations at the genus level between four bacterial communities and endometriosis. Subsequently, several associations between the gut microbiota and various subtypes of endometriosis at different anatomical sites were recognized. Specifically, three genera were linked with ovarian endometriosis, six genera were associated with tubal endometriosis, four genera showed links with pelvic peritoneum endometriosis, five genera were connected with vaginal and rectovaginal septum endometriosis, and seven genera demonstrated linkages with intestinal endometriosis. Additionally, one genus was associated with adenomyosis, and three genera exhibited associations with endometriosis-induced infertility. Our study elucidates associations between gut microbiota and site-specific endometriosis, thereby augmenting our understanding of the pathophysiology of endometriosis. Moreover, our findings pave the way for potential therapeutic strategies targeting gut microbiota for individuals grappling with endometriosis-related infertility.

Molecular mechanism of autophagy and apoptosis in endometriosis: Current understanding and future research directions.

Endometriosis is a common gynecological condition, with symptoms including pain and infertility. Regurgitated endometrial cells into the peritoneal cavity encounter hypoxia and nutrient starvation. Endometriotic cells have evolved various adaptive mechanisms to survive in this inevitable condition. These adaptations include escape from apoptosis. Autophagy, a self-degradation system, controls apoptosis during stress conditions. However, to date, the mechanisms regulating the interplay between autophagy and apoptosis are still poorly understood. In this review, we summarize the current understanding of the molecular characteristics of autophagy in endometriosis and discuss future therapeutic challenges. A search of PubMed and Google Scholar databases were used to identify relevant studies for this narrative literature review. Autophagy may be dynamically regulated through various intrinsic (e.g., PI3K/AKT/mTOR signal transduction network) and extrinsic (e.g., hypoxia and iron-mediated oxidative stress) pathways, contributing to the development and progression of endometriosis. Upregulation of mTOR expression suppresses apoptosis via inhibiting the autophagy pathway, whereas hypoxia or excess iron often inhibits apoptosis via promoting autophagy. Endometriotic cells may have acquired antiapoptotic mechanisms through unique intrinsic and extrinsic autophagy pathways to survive in changing environments.

Therapeutic Potential of Natural Resources Against Endometriosis: Current Advances and Future Perspectives.

Endometriosis (EMS) is defined as the appearance, growth, infiltration, and repeated bleeding of endometrioid tissue (glands and stroma) outside the uterus cavity, which can form nodules and masses. Endometriosis is a chronic inflammatory estrogen-dependent disease and occurs in women of reproductive age. This disorder may significantly affect the quality of life of patients. The pathogenic processes involved in the development and maintenance of endometriosis remain unclear. Current treatment options for endometriosis mainly include drug therapy and surgery. Drug therapy mainly ties to the use of non-steroidal anti-inflammatory drugs (NSAIDs) and hormonal drugs. However, these drugs may produce adverse effects when used for long-term treatment of endometriosis, such as nausea, vomiting gastrointestinal reactions, abnormal liver and kidney function, gastric ulcers, and thrombosis. Although endometriosis lesions can be surgically removed, the disease has a high recurrence rate after surgical resection, with a recurrence rate of 21.5% within 2 years and 40% to 50% within 5 years. Thus, there is an urgent need to develop alternative or additional therapies for the treatment of endometriosis. In this review, we give a systematic summary of therapeutic multiple component prescriptions (including traditional Chinese medicine and so on), bioactive crude extracts of plants/herbs and purified compounds and their newly found mechanisms reported in literature in recent years against endometriosis.