ABSTRACT
Introduction: Endometriosis (EM) is a chronic estrogen-dependent condition characterized by the growth of endometrial-like tissue outside the uterus, posing a significant burden on reproductive-aged women. Previous research has shown a correlation between gut microbiota dysbiosis and interleukin-17A (IL-17A) in EM patients. IL-17A, a promising immunomodulatory molecule, exerts dual roles in human physiology, driving inflammatory diseases. However, the functions and origins of IL-17A in EM remain poorly characterized. Methods: Single-cell data analysis was employed to characterize IL-17A activity in EM lesions. Fecal microbiota transplantation was conducted to explore the impact of gut microbiota on EM. Gut microbiota and bile acid metabolism were assessed via 16S rRNA sequencing and targeted metabolomics. Th17 cell proportions were measured using flow cytometry. Results: High expression of IL-17 receptor A (IL-17RA) was observed in myeloid cell subpopulations within EM lesions and may be involved in the migration and recruitment of inflammatory cells in lesions. Elevated IL-17A levels were further validated in peritoneal and follicular fluids of EM patients. Dysregulated bile acid levels, particularly elevated chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), were found in the gut and peritoneal fluid of EM mouse models. Additional CDCA administration reduced EM lesions and modulated Th17 cell proportions, while UDCA showed no significant effects. Discussion: Our findings shed light on the origins and functions of IL-17A in EM, implicating its involvement in lesion migration and recruitment. Dysregulated bile acid metabolism may contribute to EM pathogenesis, with CDCA exhibiting therapeutic potential.
ABSTRACT
Endometriosis is strongly associated with infertility. Several mechanisms have been reported in an attempt to elucidate the pathophysiological effects that lead to reduced fertility in women with endometriosis. However, the mechanisms by which endometriosis affects fertility have not been fully elucidated. Ferroptosis is a novel form of nonapoptotic cell death that is characterized by iron-dependent lipid peroxidation membrane damage. In past reports, elevated iron levels in ectopic lesions, peritoneal fluid and follicular fluid have been reported in patients with endometriosis. The high-iron environment is closely associated with ferroptosis, which appears to exhibit a double-edged effect on endometriosis. Ferroptosis can cause damage to ovarian granulosa cells, oocytes, and embryos, leading to endometriosis-related infertility. This article summarizes the main pathways and regulatory mechanisms of ferroptosis and explores the possible mechanisms of the formation of an iron-overloaded environment in endometriotic ectopic lesions, peritoneal fluid and follicular fluid. Finally, we reviewed recent studies on the main and potential mechanisms of ferroptosis in endometriosis and endometriosis-related infertility.
ABSTRACT
The gut microbiota (GM) has received extensive attention in recent years, and its key role in the establishment and maintenance of health and in the development of diseases has been confirmed. A strong correlation between the GM and the progression of endometriosis (EMS) has been observed in emerging research. Alterations in the composition and function of the GM have been described in many studies on EMS. In contrast, the GM in the environment of EMS, especially the GM metabolites, such as bile acids and short-chain fatty acids that are related to the pathogenesis of EMS, can promote disease progression. Chenodeoxycholic acid (CDCA), as one of the primary bile acids produced in the liver, is metabolized by various enzymes derived from the GM and is critically important in maintaining intestinal homeostasis and regulating lipid and carbohydrate metabolism and innate immunity. Given that the complexity of CDCA as a signalling molecule and the interaction between the GM and EMS have not been clarified, the role of the CDCA and GM in EMS should be understood from a novel perspective. However, few articles on the relationship between CDCA and EMS have been reviewed. Therefore, we review the available and possible potential links between CDCA, the GM and EMS and put forward the hypothesis that CDCA and its derivative obeticholic acid can improve the symptoms of EMS through the GM.
ABSTRACT
Background: Gut microbiota is a complex ecosystem that is vital for the development and function of the immune system, is closely associated with host immunity, and affects human health and disease. Therefore, the current progress and trends in this field must be explored. Purpose: No bibliometric analysis has been conducted on gut microbiota and host immune response. This study aimed to analyze the current progress and developing trends in this field through bibliometric and visual analysis. Methods: Global publications on gut microbiota and host immune response from January 2011 to December 2021 were extracted from the Web of Science (WOS) collection database. GraphPad Prism, VOSviewer software, and CiteSpace were employed to perform a bibliometric and visual study. Results: The number of publications has rapidly increased in the last decade but has declined in the most recent year. The Cooperation network shows that the United States, Harvard Medical School, and Frontiers in Immunology were the most active country, institute, and journal in this field, respectively. Co-occurrence analysis divided all keywords into four clusters: people, animals, cells, and diseases. The latest keyword within all clusters was "COVID," and the most frequently occurring keyword was "SCFA." Conclusion: Gut microbiota and host immune response remain a research hotspot, and their relation to cancer, CNS disorders, and autoimmune disease has been explored. However, additional studies on gut microbiota must be performed, particularly its association with bacterial strain screening and personalized therapy.
ABSTRACT
Endometriosis (EMs) occurs in approximately 50% of women with infertility. The main causes of EMs-related infertility are follicle dysplasia and reduced oocyte quality. Iron overload occurs in ovarian follicular fluid (FF) of patients with EMs, and this condition is associated with oocyte maturation disorder. However, the underlying molecular mechanism remains largely unknown. In the present study, we identified the mechanism underlying ferroptosis in ovarian granulosa cells and oocyte maturation failure in EMs based on a retrospective review of in vitro fertilization/intracytoplasmic sperm injection-frozen embryo transfer outcomes in infertile patients with EMs. Mouse granulosa cells were treated with EMs-related infertile patients' follicular fluid (EMFF) in vitro. Western blot analysis, quantitative polymerase chain reaction, fluorescence staining, and transmission electron microscopy were used to assess granulosa cells ferroptosis. The effects of exosomes were examined by nanoparticle tracking analysis, RNA-seq, and Western blot analysis. Finally, the therapeutic values of vitamin E and iron chelator (deferoxamine mesylate) in vivo were evaluated in an EMs-related infertility model. Patients with ovarian EMs experienced poorer oocyte fertility than patients with non-ovarian EMs. We observed that EMFF with iron overload-induced granulosa cell ferroptosis in vitro and in vivo. Mechanically, nuclear receptor coactivator four-dependent ferritinophagy was involved in this process. Notably, granulosa cells undergoing ferroptosis further suppressed oocyte maturation by releasing exosomes from granulosa cells. In therapeutic studies, vitamin E and iron chelators effectively alleviated EMs-related infertility models. Our study indicates a novel mechanism through which EMFF with iron overload induces ferroptosis of granulosa cells and oocyte dysmaturity in EMs-related infertility, providing a potential therapeutic strategy for EMs-related infertility.
