Role of eutopic endometrium in pelvic endometriosis

Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity and is considered a benign gynecologic condition; however, in some cases, it may be aggressive. The pathogenesis of endometriosis is complex and multifactorial. Despite being one of the most widely studied gynecologic diseases, its pathogenesis remains uncertain. The intrinsic endometrial abnormalities thought to be associated with endometriosis include abnormal expression of genes, modification of endometrial response to hormones such as progesterone; increased nerve density, and oxidative stress. Evaluation of the endometrium in patients with endometriosis is an important line of investigation in the pathophysiology of the disease. It has been suggested that investigation of eutopic endometrium may help to achieve this goal. Presented herein is a literature review and a comprehensive evaluation of the role of eutopic endometrium in pelvic endometriosis. Clinical correlations of the disease are highlighted, with the objective of understanding the role of eutopic endometrium in endometriosis.     

Cell proliferation in endometrium of women with endometriosis

The purpose of this study was to describe the endothelial cell activity of the endometrial tissue in women with and without endometriosis, and find out the diagnostic opportunities for everyday gynecologic practice. There were 30 women with laparoscopic proved endometriosis involved in our study and 27 women with no endometriosis used as a control group. The histological findings were scored after Noyes criteria and classified according to the phase of the menstrual cycle. We found out a significant difference between the two groups, especially during the proliferate phase of the menstrual cycle.     

Effect of gestrinone in endometriosis tissue and endometrium

The effects of gestrinone (R 2323) on endometrial and endometriosis tissue concentrations of cytosol estrogen and progestin receptors and the activity of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) were investigated in 11 patients operated on because of suspected external endometriosis. Serum concentrations of luteinizing hormone, follicle-stimulating hormone, estradiol (E2), progesterone, testosterone (T), and sex-hormone-binding globulin (SHBG) were also investigated. After one control cycle, the patients received 2.5 mg of oral gestrinone twice weekly from the fifth day of the first treatment cycle until the eighth day of the second treatment cycle, the day of operation being day 10. Treatment with gestrinone decreased serum concentrations of T during the second treatment cycle and effected a major decrease in SHBG during both treatment cycles, resulting in highly increased free T and free E2 indices. The effects of gestrinone on the endometrium, a decrease in estrogen and progestin receptors, and induction of 17 beta-HSD are characteristic progestin actions. These parameters remained unchanged in endometriosis tissue. Our data indicate that gestrinone has effects that are typical of androgens and progestins in patients with endometriosis.     

趋化因子受体6在子宫内膜异位症在位内膜及异位灶中的表达

目的分析趋化因子受体6(chemokine receptor,CCR6)在子宫内膜异位症(内异症)患者的在位内膜及异位内膜中的表达水平,以探讨其在发病中的作用。方法采用免疫组化技术检测内异症患者在位内膜及异位灶CCR6的表达。结果对照组子宫内膜中CCR6的表达分泌期明显强于增殖期(P0.05);内异症患者在位子宫内膜间质和腺体CCR6的表达比较,差异无统计学意义(P0.05),但其表达强度高于对照组(P0.05),异位灶CCR6的表达明显高于对照组(P0.05),略高于在位子宫内膜,但无统计学意义(P0.05)。结论CCR6的表达具有周期特异性,可能受雌/孕激素调节,参与子宫内膜异位症的发生和进展。     

Differential expression of claudins in human endometrium and endometriosis

Membrane proteins of the claudin superfamily are important components of cellular tight and adherens junctions. Although their exact function remains unclear, these proteins may play a role in tissue remodeling, a process which is associated with several diseases including endometriosis. In the present work we analyzed the expression of 13 members of the claudin family in the endometrium and peritoneum by microarray analysis. Real-time polymerase chain reaction and immunohistochemistry in human endometrium and peritoneal endometriotic lesions were performed for validation of the expression of claudin-1, -3, -4, -5 and -7. Diminished expression of claudin-3, -4 and -7 in ectopic endometrium was frequently observed as indicated by all three methods. In contrast to a higher expression of claudin-5 mRNA detected in bulk biopsies of ectopic endometrium, immunohistochemistry revealed no alteration of claudin-5 protein expression in glandular cells of endometriosis samples. The downregulation of various members of the claudin family may contribute to endometrial cell detachment and increase the number of cells invading pelvic organs.     

Immunohistochemical study of angiogenic factors in endometrium and endometriosis

The proliferative activity and angiogenic factors of pelvic endometriosis and uterine endometrium and their correlation with different pigmented lesions are important throughout the menstrual cycle. The proliferative activity and/or expression of angiogenic factors appears to be different between endometrium and endometriosis, and also different in each pigmented lesion. Immunohistochemical studies using computerized image analysis have shown that in normal endometrium, the PCNA index shows cyclic variation, but no cyclic change is observed in endometriosis. In the pelvic peritoneum, the PCNA index is higher in red lesions compared to black and white lesions. There is no difference in VEGF expression among different pigmented lesions. However, a cyclic variation of VEGF concentration was found in the peritoneal fluid of patients with endometriosis. As a newly determined angiogenic factor, the number of endoglin-positive cells and the mean endothelial area were higher in red lesions than in black or white lesions. These results suggest that the pathogenesis and activity of endometriosis possibly depends on internal angiogenesis. The cellular activity of endometriotic lesions may not necessarily coincide with the regulation of angiogenesis, and may not be synchronized in each pigmented pelvic lesion of endometriosis. Copyrightz1999S.KargerAG, Basel     

Immunoglobulin content of the endometrium in women with endometriosis

A study of the immunoglobulin content of endometria from women with and without endometriosis has shown that, in women with endometriosis, both IgG and IgA are more commonly found in the interstitium of the endometrial stroma than is the case in endometria from women without this disease. It is thought that the increased stromal content of immunoglobulins in endometriosis is simply a passive reflection of elevated serum IgG and IgA levels. Both the incidence and extent of positive endometrial glandular epithelial staining for IgG and IgA are markedly increased in women with endometriosis: the excess of intraepithelial IgA is probably simply a consequence of the excess of stromal IgA, but the increased epithelial staining for IgG lends support to the concept that many women with endometriosis develop autoantibodies directed against an endometrial epithelial antigen. No relationship could be demonstrated, however, between IgG deposition in the endometrium of women with endometriosis and a history of infertility.     

The role of prostaglandin E2 in endometriosis

Endometriosis is a leading cause of infertility in women of reproductive age. It involves the occurrence of endometrial tissue outside the uterine endometrium, mainly in the peritoneal cavity. Prostaglandin E(2) is up regulated in the peritoneal cavity in endometriosis and is produced by macrophages and ectopic endometrial cells. This prostaglandin is involved in the pathophysiology of the disease and elicits cell signals via four receptor types. Prostaglandin E(2) increases estrogen synthesis by up regulating steroidogenic acute regulatory protein (StAR) and aromatase. It inhibits apoptosis and up regulates fibroblast growth factor-9 (FGF-9) promoting cell proliferation. Prostaglandin E(2) affects leukocyte populations and promotes angiogenesis through its effect on estrogen and up regulation of vascular endothelial growth factor (VEGF). Dienogest is a synthetic progestin targeting expression of genes involved in prostaglandin synthesis.     

EG-VEGF在正常子宫内膜及子宫内膜异位症的表达研究

目的 探讨内分泌腺特异性血管内皮生长因子（EG—VEGF）在子宫内膜异位症（EM）的表达及其在EM发生发展中的作用。方法 采用RT—PCR检测并比较VEGF mRNA和EG—VEGF mRNA在EM异位内膜和对照组正常内膜的表达及其相关性。结果 ①EM异位内膜的VEGF mRNA相对量（0．68±0．48）明显高于对照内膜（0．16±0．55）（P〈0．05）；但异位内膜的EG—VEGF mRNA相对量（0．05±0．56）与对照组内膜（0.025±0．25）相比，差异无显著性（P〉0．05）；②EM异位内膜的VEGF mRNA和EG—VEGF mRNA相对量相关性分析表明无相关性（P〉0．05）；与正常对照内膜的结果相同。结论 EG—VEGF在EM有一定表达，但作用机制有待进一步研究。     

Apoptosis expression in rats' endometrium after surgical induction of endometriosis

OBJECTIVES: Endometriosis is characterised as a presence of proliferating endometrial fragments growing outside uterus. Despite many investigations we still do not understand why in some women sheded endometrium implants itself into peritoneum and grows, and in the others does not. It is possible that apoptotic status of endometrial fragments implanted into peritoneum is responsible for endometriosis growth as well as the treatment results. Cellular apoptosis is characterised morphologically by cell shrinkage, nuclear pyknosis, chromatin condensation, and blebbing of the plasma membrane. MATERIAL AND METHODS: The study was performed on 28 mature Wistar rats. We studied endometria of rats after induction of endometriosis in peritoneal cavity. RESULTS: The only difference was found in endometrial glands. In animals with successful endometriosis implantation apoptosis indices in endometrial glands obtained during second laparotomy were lower than in the endometriosis free animals (p < 0.05).     

Apoptosis pattern in human endometrium in women with pelvic endometriosis

OBJECTIVE: In the present study we aimed to describe apoptosis patterns in eutopic endometrium in women suffering from endometriosis in order to assess its value as a marker of early forms of endometriosis, and also to try to answer whether endometriosis is caused by changes within the eutopic endometrium or whether endometriotic lesions change the characteristics of eutopic endometrium. STUDY DESIGN: The study was performed on 125 women treated in Division of Reproduction. In 52 patients peritoneal endometriosis was diagnosed (I(0)-23; II(0)-29). Seventy-three patients in whom no endometriotic foci could be found at laparoscopy were qualified as the control group. Endometrial biopsy 7-9 days after ovulation was taken for assessment of apoptosis (TUNEL) and routine histology. RESULTS: Apoptosis indices in the eutopic endometrium of women with endometriosis were lower compared to women without endometriosis. In the endometrial glands apoptosis indices were 2.94+/-1.66 versus 5.23+/-2.06 (p<0.01) in the group of women with and without endometriosis, respectively. In the endometrial stroma apoptosis indices were estimated at 2.04+/-1.72 in women with endometriosis and 4.12+/-1.62 in the control group (p<0.01). CONCLUSIONS: The observed changes could support the hypothesis of the different properties of eutopic endometrium in endometriotic women as a causing factor of peritoneal endometriosis.     

The role of iron in the pathogenesis of endometriosis

Background.?Endometriosis may cause symptoms including chronic pelvic pain and infertility, and increases susceptibility to the development of ovarian cancer. Genomic studies have started to delineate the wide array of mediators involved in the development of endometriosis. Understanding the mechanisms of endometriosis development and elucidating its pathogenesis and pathophysiology are intrinsic to prevention and the search for effective therapies.

Method of study.?The present article reviews the English language literature for biological, pathogenetic and pathophysiological studies on endometriosis. Several recent genomic studies are discussed in the context of endometriosis biology.

Results.?Severe hemolysis occurring during the development of endometriosis results in high levels of free heme and iron. These compounds oxidatively modify lipids and proteins, leading to cell and DNA damage, and subsequently fibrosis development. Recent studies based on genome-wide expression analysis technology have noted specific expression of heme/iron-dependent mediators in endometriosis. The heme/iron-dependent signaling pathway of endometriosis, which is providing new insights into the regulation of inflammation, detoxification and survival, is discussed.

Conclusion.?Several important endometriosis-specific genes overlap with those known to be regulated by iron. Other genes are involved in oxidative stress. Iron has a significant impact on endometriotic-cell gene expression. This review summarizes recent advances in the heme/iron-mediated signaling and its target genes, outlines the potential challenges to understanding of the pathogenesis and pathophysiology of endometriosis, and proposes a possible novel model.     

Cyclooxygenase-2 expression in deep endometriosis and matched eutopic endometrium

OBJECTIVE: To identify any relationship between cyclooxygenase-2 expression and the intensity of severe, endometriosis-related dysmenorrhea. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Patients with deep endometriosis. INTERVENTION(S): During surgery, paired samples of tissue representing deep endometriosis and eutopic endometrium were obtained from 46 patients. Control endometrial tissue samples were obtained from 34 fertile women who underwent laparoscopic tubal ligation or reversal of tubal sterilization. Pain assessment for dysmenorrhea was done with a 10-point linear analogue scale. MAIN OUTCOME MEASURE(S): The percentage of surface immunostained for Cox-2 was determined by an immunohistochemical technique. Relationships between pain score for dysmenorrhea and Cox-2 expression were analyzed. RESULT(S): Cox-2 expression was significantly higher in eutopic endometrial stromal cells from patients with deep endometriosis than in stroma from controls during the early, mid, and late secretory phases. In endometriosis patients, Cox-2 expression in eutopic endometrial stromal cells was significantly higher in women with more severe dysmenorrhea (pain score > or =7 vs. <7) during early and mid secretory phases. CONCLUSION(S): Elevated Cox-2 expression in stromal cells in eutopic endometrium from patients with deep endometriosis may play a role in severe, endometriosis-related dysmenorrhea.     

VEGF在子宫内膜异位症发病机制中的作用

目的:探讨血管内皮生长因子(Vascular endothelial growth factor,VEGF)在子宫内膜异位症(Endometriosis,EMs)组织中的表达及其在EMs发生发展中的作用。方法:采用ELISA法检测30例EMs患者(研究组)和16例子宫肌瘤患者(对照组)血清和腹腔液中的VEGF水平,免疫组化和RT-PCR检测并比较VEGF蛋白、VEGF mRNA在EMs异位内膜、在位内膜和对照组正常内膜的表达及其相关性。结果:EMs患者腹腔液、异位内膜、在位内膜VEGF蛋白及mRNA均明显高于对照组(P<0.05),但与EMs临床分期无关。EMs患者血清VEGF与对照组相比无明显的差异(P>0.05)。EMs患者异位内膜和在位内膜的微血管密度(MVD)明显高于对照组内膜(P<0.05)。结论:VEGF在EMs患者的高表达,说明其通过促血管生成在该病发生发展中起着重要作用。     

子宫内膜异位症在位和异位内膜的MMPS活性分析

目的 分析子宫内膜异位症(EM)患者在位及异位子宫内膜中活化型基质蛋白酶-2、-9(MMP-2、MMP-9)、非活化型基质蛋白酶12、19(proMMPl2、proMMP-9)的酶谱及在EM发病机制中的作用。方法 2000年3月至2002年9月采用酶谱法检测16例手术治疗EM患者的异位内膜和在位内膜，16例同期住院的月经正常的良性卵巢肿瘤或子宫肌瘤的子宫内膜中的pmMMP-2、MMP-2、proMMP-9、MMP-9。结果 EM同一个体的异位内膜proMMP-2、proMMP-9活性高于在位内膜；在位内膜的proMMP-9活性无论何期明显高于对照组正常的子宫内膜；proMMP-2活性在增生期在位内膜较对照组正常内膜有上升趋势。而MMP-2及MMP-9均未见规律性趋势。结论 同一个体的异位内膜的proMMP-2、pmMMP-9活性较在位内膜增高，提示异位内膜更具侵蚀性。同为在位内膜，EM的proMMp-9活性较正常对照为高，可能与EM的发病有关。而proMMP-2活性仅在增生期表现在位内膜较对照组正常为高，可能提示增生期内膜更具侵蚀性。