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Abstract：
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, 4.0 µM of EDM can efficiently reverse this effect in in vitro cell culture studies. Additionally, 20 mg/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.
摘要：
简介：子宫内膜异位症（EMS）的特征是一种普遍存在的妇科炎症疾病，其特征是子宫外存在子宫内膜组织。这种情况会导致持续的盆腔疼痛，并可能导致不孕。在这次调查中,我们探讨了在小鼠模型中短暂暴露于潜伏膜蛋白1(LMP1)或EB病毒(EBV)引发子宫内膜异位症(EMS)发生的潜在机制.此外,我们研究了evodiamine（EDM）对EMS的潜在抑制作用。方法：将永生化人子宫内膜基质细胞（HESC）或上皮细胞（HEEC）瞬时暴露于EBV或LMP1。评估evodiamine（EDM）的存在对雌激素受体β（ERβ）表达的影响，以及细胞代谢参数，如氧化还原平衡，线粒体功能，炎症,和扩散。此外,腹膜内施用LMP1处理的HESC和HEEC的混合物以产生EMS小鼠模型.采用不同剂量的EDM进行治疗，以评估其对EMS发展的潜在抑制作用。结果：瞬时暴露于EBV或LMP1通过表观遗传修饰触发持续的ERβ表达，随后调节相关细胞代谢以促进EMS发育。此外，在体外细胞培养研究中，4.0µM的EDM可以有效地逆转这种作用。此外,20mg/kg体重的EDM治疗可以部分抑制体内EMS小鼠模型中的EMS发展。结论：瞬时EBV/LMP1暴露引发永久性ERβ表达，有利于后期EMS开发，EDM通过ERβ抑制抑制EMS发展。这提出了一种新的成年子宫内膜异位症（EMS）发展机制，该机制源于儿童期早期爱泼斯坦-巴尔病毒（EBV）暴露。此外，evodiamine（EDM）是治疗EMS的潜在候选药物。
