青春期子宫内膜异位症的发病特点研究进展

青春期子宫内膜异位症(EMs)是EMs的一种特殊类型,与育龄期妇女相似,可引起痛经、慢性盆腔痛、不孕等症状。该病发病原因不明确,发病机制复杂多样,目前学说认为与经血逆流、遗传、血源播散等因素相关。其中逆流经血中包含子宫内膜样干细胞的观点近年来引发热议,即子宫内膜样干细胞通过经血逆流入腹腔,发生异位种植、侵袭、生长,从而导致EMs。目前诊断EMs的金标准为腹腔镜手术及病理检查,但由于发病时间早,且易于复发,是妇科的一个棘手问题。综述青春期EMs的流行病学资料、发病机制、相关高危因素及临床特点,继续深入研究有助于加强对青春期EMs的预防,做到早诊断,早治疗,减少日后EMs并发症的发生。     

干细胞与子宫内膜异位症

子宫内膜异位症（endometriosis,EMs）至今病因不明确,其发病机制有子宫内膜种植学说、体腔上皮化生学说、免疫学说等多种学说。随着干细胞相关研究的不断深入,多项研究均证明子宫内膜内存在着干,祖细胞,可能来源于胚胎残留干细胞或骨髓来源干细胞,这些干,祖细胞介导了子宫内膜的周期性再生。进一步提出EMs干细胞起源学说,认为子宫内膜干,祖细胞异常分化增殖可能导致EMs发生,即EMs是一种干细胞相关疾病。各种来源的干细胞是“种子”,而逆流经血及局部微环境提供“土壤”,只要局部组织中同时存在“种子”和“土壤”,EMs就会发生。为EMs的发病机制及临床诊疗研究提供新思维。     

干细胞与子宫内膜异位症

子宫内膜异位症(endometriosis,EMs)至今病因不明确,其发病机制有子宫内膜种植学说、体腔上皮化生学说、免疫学说等多种学说.随着干细胞相关研究的不断深入,多项研究均证明子宫内膜内存在着干/祖细胞,可能来源于胚胎残留干细胞或骨髓来源干细胞,这些干/祖细胞介导了子宫内膜的周期性再生.进一步提出EMs干细胞起源学说,认为子宫内膜干/祖细胞异常分化增殖可能导致EMs发生,即EMs是一种干细胞相关疾病.各种来源的于细胞是"种子",而逆流经血及局部微环境提供"土壤",只要局部组织中同时存在"种子"和"土壤",EMs就会发生.为EMs的发病机制及临床诊疗研究提供新思维.     

青春期子宫内膜异位症诊治的研究进展

子宫内膜异位症（endometriosis,EMs）指子宫内膜腺体和间质出现在子宫腔以外部位的一类妇科疾病,可影响女性整个生命周期。青春期EMs作为一种特殊年龄段的EMs,正日益受到关注。青春期EMs发病的主要危险因素包括遗传易感性、梗阻性生殖道畸形与内源性雌激素升高等。其发病机制假说众多,包括经血逆流学说、体腔上皮化生、血源性扩散、淋巴扩散、新生儿子宫出血和免疫学学说等。青春期EMs的诊断需综合临床症状、体征、血清学、影像学、手术及病理组织学结果。个性化的内外科治疗被认为是缓解症状、抑制疾病进展、保护未来生育力的最有效的治疗策略。综述青春期EMs的危险因素、发病机制、临床表现及诊治方式,以期为临床医生对该病的认识和诊治提供参考。     

干细胞在子宫内膜异位症发病中的意义

子宫内膜异位症(endometriosis,EMs)是多因素疾病,至今病因不明。研究证明,子宫内膜存在干/祖细胞,包括胚胎残留干细胞或骨髓来源干细胞,这些干/祖细胞介导子宫内膜的周期性再生。越来越多的研究通过寻找特异性干细胞标记物以分离并鉴定子宫内膜干/祖细胞,并提出了EMs的干细胞起源学说,认为子宫内膜干/祖细胞异常分化增殖可能导致EMs发生。各种来源的干细胞是"种子",而逆流经血、雌激素治疗及局部微环境是"土壤",只要局部组织同时存在"种子"和"土壤",EMs就会发生。这一学说为EMs发病机制及临床诊疗研究提供了新思路。     

子宫内膜异位症与干细胞学说

子宫内膜异位症(endometriosis,EMs)是一种妇科常见的疑难病。其发病机制存在多种学说:子宫内膜种植学说、体腔上皮化生学说、胚胎剩余学说、淋巴血管转移学说、诱导学说以及最近的"在位内膜决定论",但这些学说均不能完全解释临床上多种类型EMs的发病机制。近年,越来越多的学者提出了EMs的干细胞学说,当经血逆流后,盆腔内环境、雌激素的作用等因素,为种植的内膜碎片中未分化干细胞、胚胎期遗留下的干细胞、骨髓干细胞和种植部位组织中未分化干细胞提供了分化的内环境。综述近年的EMs与干细胞学说的相关研究。     

干细胞与子宫内膜异位症发病机制的研究进展

子宫内膜异位症(endometriosis,EMs)在育龄妇女中的发病率近15%,其发病机制一直是研究的热点,经典的"经血逆流与种植学说"不断受到挑战,无法解释如盆腔外远处病灶及特殊部位异位病灶的发生等问题,而干细胞学说尝试从"一元论"角度解释所有类型异位病灶的发生。参与EMs异位病灶的干细胞可能来源于子宫内膜、骨髓、卵巢及其他来源。而雌激素、趋化因子、表皮生长因子、血小板源性生长因子等多种因子参与成体干细胞的分化。微小RNA水平与表观遗传学改变可能参与调控间充质干细胞向子宫内膜样细胞的分化过程。异常定植的干细胞可能改变子宫的容受性,导致不孕、流产等不良生育结局。在形成的不同类型EMs病灶中,腹膜型与深部浸润型病灶干细胞基因表达相似,而与在位内膜干细胞基因表达存在差异。随着研究的不断深入,干细胞在妇产科领域的应用越来越广,在治疗卵巢功能早衰、Asherman综合征、EMs相关性不孕及靶向药物研发方面前景广阔。     

干细胞与子宫内膜异位症发病机制的研究进展

子宫内膜异位症（endometriosis,EMs）在育龄妇女中的发病率近15%,其发病机制一直是研究的热点,经典的“经血逆流与种植学说”不断受到挑战,无法解释如盆腔外远处病灶及特殊部位异位病灶的发生等问题,而干细胞学说尝试从“一元论”角度解释所有类型异位病灶的发生。参与EMs异位病灶的干细胞可能来源于子宫内膜、骨髓、卵巢及其他来源。而雌激素、趋化因子、表皮生长因子、血小板源性生长因子等多种因子参与成体干细胞的分化。微小RNA水平与表观遗传学改变可能参与调控间充质干细胞向子宫内膜样细胞的分化过程。异常定植的干细胞可能改变子宫的容受性,导致不孕、流产等不良生育结局。在形成的不同类型EMs病灶中,腹膜型与深部浸润型病灶干细胞基因表达相似,而与在位内膜干细胞基因表达存在差异。随着研究的不断深入,干细胞在妇产科领域的应用越来越广,在治疗卵巢功能早衰、Asherman综合征、EMs相关性不孕及靶向药物研发方面前景广阔。     

子宫内膜干细胞在子宫内膜异位症发病中意义

子宫内膜异位症(EMs)发病是多因素的。越来越多的研究尝试着分离并界定出人类子宫内膜干/祖细胞,且这些干细胞可能定位于基底层的间质中。目前仍未找到独特的鉴定子宫内膜干细胞的标志物。子宫内膜可能存在至少两种干细胞,包括子宫来源或骨髓来源的干细胞,其可经逆流的经血或经循环迁移至异地,并在特定的微环境中形成EMs病灶,这表明EMs可能是一种干细胞疾病。     

血管生成及抗血管生成与子宫内膜异位症关系研究进展

子宫内膜异位症(endometriosis,EMs)发病机制迄今尚未明确,主要包括经血逆流种植学说、淋巴及静脉播散学说、体腔上皮化生学说、诱导学说、遗传学说、环境及免疫学说。郎氏"在位内膜决定论"及近年多项研究显示,EMs可能是一种干细胞疾病[1-2]。对各种发病机制研究发现,血管生成是异位病灶种植和增殖的必要条件。     

Immunology of endometriosis

Endometriosis is classically described as the presence of both endometrial glandular and stromal cells outside the uterine cavity, mainly in the pelvis. The pathogenesis of this enigmatic disorder still remains controversial despite extensive research. Although multiple theories have been put forth to explain the pathophysiology and pathogenesis of endometriosis, the retrograde menstruation theory of Sampson is the most widely accepted. However, since retrograde menstruation occurs in most of the reproductive age women, it is clear that there must be other factors which may contribute to the implantation of endometrial cells and their subsequent development into endometriotic disease. There is substantial evidence to support that the alterations in both cell-mediated and humoral immunity contribute to the pathogenesis of endometriosis. Increased number and activation of peritoneal macrophages, decreased T cell and natural killer (NK) cell cytotoxicities are the alterations in cellular immunity and result in inadequate removal of ectopic endometrial cells from the peritoneal cavity. Moreover, increased levels of several cytokines and growth factors which are secreted by either immune and endometrial cells seem to promote implantation and growth of ectopic endometrium by inducing proliferation and angiogenesis. In addition to the impaired capacity of the immune cells to mediate endometrial cell removal, inherent resistance of the ectopic endometrial cells against immune cells is another interesting concept in the pathogenesis of endometriosis. Endometriosis has also been considered to be an autoimmune disease, since it is often associated with the presence of autoantibodies, other autoimmune diseases, and possibly with recurrent immune-mediated abortion.     

Endometrial stem/progenitor cells and their role in the pathogenesis of endometriosis

Human endometrium regenerates on a cyclical basis each month, likely mediated by endometrial stem/progenitor cells. Several types of stem/progenitor cells have been identified: CD140b⁺CD146⁺ or SUSD2⁺ endometrial mesenchymal stem cells (eMSCs), N-cadherin⁺ endometrial epithelial progenitor cells (eEPs), and side population (SP) cells, a heterogeneous population predominantly comprising endothelial cells. eMSCs reside in a perivascular niche and likely mediate angiogenesis and stromal regeneration. Human eEPs are located in the bases of glands in the basalis and are likely more primitive than SSEA-1⁺ basalis epithelial cells. Endometrial stem/progenitor cells may contribute to the pathogenesis of endometriosis by their retrograde shedding into the pelvic cavity, either after menarche or as a result of neonatal uterine bleeding. eMSCs may have a role in the generation of progesterone-resistant phenotype of endometrial stromal fibroblasts (eSFs) in endometriosis. In future clinical practice, endometrial stem/progenitor cells may be used to establish diagnosis of endometriosis or as therapeutic targets.     

Endometriosis: etiology and pathophysiology of infertility

The risk for developing endometriosis begins at puberty and extends to menopause in women of all races. The major pathway in the pathogenesis of this disease is the transplantation of endometrial cells to the pelvis and other abdominal organs via retrograde menstruation. Although retrograde menstruation appears to be a near universal occurrence, those women who are at particular risk for developing the disease have menstrual characteristics that increase the amount and duration of menstrual contamination of the pelvis. The ability of the body's immune system to remove this debris may play a significant independent role. In spite of the apparent association of infertility and endometriosis, there is a paucity of evidence to identify a clear cause-and-effect relationship or to clarify the specific mechanism(s) of infertility due to this enigmatic disease. Areas that warrant additional attention include the effect of endometriosis on ovulation, the impact of the immune system on the development of endometriosis, and the effect of peritoneal inflammation on reproduction. A better understanding of these areas will lead to more efficacious and specific therapies for endometriosis-associated infertility.     

Serum VEGF (vascular endothelial growth factor) concentration in patients with endometriosis

The theory of Sampson that endometrial cells and fragments desquamated during the menstrual period are transported through fallopian tubes into the peritoneal cavity where they implant, proliferate and develop into endometriotic lesions is generally accepted. Accumulating data suggest that deficient immunity against retrograde endometrium during menstruation may be involved in the pathophysiology of endometriosis. Recent studies in women with endometriosis demonstrated functional changes in several immunologic components in the peritoneal fluid as well as in sera of those patients. Among others it was shown that a wild pattern of cytokines take part in events occurring during endometrial cells implantation, proliferation and forming of endometriotic lesions. One of them VEGF seems to play a very important role in neovascularisation and implantation of ectopic endometrial lesions. In present study we evaluated the concentrations of VEGF in serum of patients with endometriosis and showed negative correlation between AFS score and VEGF concentration in peritoneal endometriosis. Above results do not confirm former observations indicating the role of VEGF in endometriosis pathogenesis.     

New considerations for the pathogenesis of endometriosis.

OBJECTIVES: To review the available evidence regarding the immunological, epidemiological and other factors involved in the pathogenesis of endometriosis. METHODS: Literature review. RESULTS: Endometriosis remains a poorly-understood disease of unknown etiology and pathogenesis. CONCLUSIONS: There is evidence to suggest that alterations in the immune response, whether genetically transmitted or environmentally induced, predispose women to the ectopic implantation of endometrial cells transported into the peritoneal cavity by way of retrograde menstruation. This predisposition may exist because of an impaired peritoneal clearing of endometrial cells and fragments or because of pathological angiogenesis.     

Stammzellen im Endometrium

In recent years the concept of adult stem cells mediating cyclic endometrial regeneration has become increasingly accepted. This hypothesis is supported by the identification of endometrial expression of stem cell markers such as Oct-4, Musashi-1 and telomerase, and by demonstration of the multi-lineage differentiation potential of clonal endometrial cells. Adult stem cells only represent a small percentage of all stromal and glandular cells of the endometrium; therefore, identification of additional specific markers to further characterize these cells is needed. A dysregulation of stem cell function is implicated in the pathogenesis of proliferative diseases of the endometrium, including endometriosis, the growth of ectopic endometrial tissue outside the uterine cavity. An induced differentiation of these cells may prove to be a fruitful therapeutic concept in the near future. Apart from endometrial tissue stem cells, bone marrow-derived stem cells have been identified in the endometrium, in addition to menstrual blood-derived stem cells. The latter may expand therapeutic options in regenerative medicine, e. g. for patients suffering from myocardial infarction.     

The role of endometrium in endometriosis

Endometriosis is defined as the presence of endometrial glands and stroma outside the uterus. Several theories have been proposed to explain the pathogenesis of this disease. According to Sampson's retrograde menstruation theory, endometrial cells are refluxed through the fallopian tubes during the menstruation and implant onto peritoneum or pelvic organs. Since retrograde menstruation is a very common phenomenon among women of reproductive age, there must be other factors that may contribute to the pathophysiology and/or pathogenesis of endometriosis. Genetic predisposition, environmental factors, and alterations in immune and endocrine functions are believed to play significant roles in the establishment and maintenance of endometriosis. Although the eutopic endometriums of women with and without endometriosis are histologically similar, studies revealed that there are many fundamental differences between these two tissues. Invasive properties, decreased apoptosis, alterations in expression of specific gene and proteins, and increased steroid and cytokine production have been identified in eutopic endometrium of women with endometriosis. Furthermore, significant biochemical differences exist even between ectopic and autologous eutopic endometrium. These differences can be explained by the direct effects of an inflammatory peritoneal environment.