子宫内膜异位症人体组织学模型构建及内异症和非内异症患者子宫内膜粘附特点分析
摘要
子宫内膜异位症人体组织学模型构建及内异症和非内异症患者子宫内膜粘附特点分析
研究背景
子宫内膜异位症(Endometriosis，简称内异症)是育龄妇女的多发病。它所引起的痛经、下腹痛和不孕严重影响妇女的健康和生活质量。目前发病机制不清，治疗对策有限。
在内异症诸多的发病学说中，Sampson的经血逆流学说是主导理论，但其难以解释经血逆流现象中仅小部分形成内异症以及盆腹腔以外内异症的问题。新近的研究提示，造成这一现象的原因是内异症的在位内膜与正常人相比，具有诸如超微结构、基因、表达产物和机能状态的差异。
模型建立是研究内异症的重要手段。尽管已成功构建了多种内异症模型，但仍然存在一些不足，如细胞模型与人体生理状况有较大差别，不能反映人体各种细胞间相互影响的错综复杂的关系；动物模型的模拟程度一直为一些学者所批评，认为内异症是人类和非人类灵长类动物(包括猕猴和狒狒等)所特有的一种疾病，而大多数动物模型所选择的啮齿类动物和兔等无周期性月经，不发生子宫内膜异位症，用其构建内异症模型并不合理。而最理想的动物模型包括猕猴和狒狒等因其来源稀缺、价格昂贵，可行性受到了很大限制。
子宫内膜异位症人体组织学模型是近10年来出现的一种新型模型。其建模方法是用人子宫内膜组织体外分离成组织碎片后接种于腹膜组织间皮面共培养以探索子宫内膜异位症的发病机制。它的优点在于：①模拟程度高：它直接反映了人体子宫内膜与人体腹膜的相互作用，模拟内异症的早期发病过程；②可动态观察内异症患者在发病早期在位内膜与腹膜组织粘附、侵袭并形成新生血管的连续过程，得到直接组织学证据；③可比较分析内异症和非内异症患者在位内膜和腹膜的异同，为进一步探索病因提供途径；④资源丰富，可行性好。但是，迄今为止，关于此模型的研究均为定性研究，且各家培养条件不一，结果差异也较大；尚未有研究涉及到定量分析。
研究目的
1、探索子宫内膜组织培养条件及子宫内膜组织与腹膜组织粘附的培养条件。
2、分析子宫内膜与腹膜粘附的细胞学行为及分子生物学表现。
3、对比研究内异症和非内异症患者子宫内膜与腹膜的粘附特点。
研究方法
1、比观察气液面培养和培养基中培养对于子宫内膜组织及子宫内膜组织粘附腹膜的影响。
2、子宫内膜接种腹膜后在培养的不同时间点收集标本用光镜观察子宫内膜与腹膜粘附发生的时间，粘附部位的细胞学行为。
3、免疫组化和免疫荧光方法鉴别粘附部位各种细胞及ELISA检测培养基中sICAM-1、MMP-2和VEGF的分泌。
4、电镜观察内异症和非内异症患者的子宫内膜组织和腹膜组织的异同。
5、振荡试验、光镜和电镜观察内异症和非内异症患者的子宫内膜与腹膜自身及交叉接种后各组间粘附的异同。
6、进行内异症和非内异症患者的子宫内膜组织培养，ELISA检测培养基中sICAM-1的分泌规律。
结果
1、子宫内膜组织气液平面培养较培养基中培养组织结构维持好，离体培养时间长。
2、子宫内膜组织和腹膜组织在气液平面培养能较早发生粘附和侵袭。
3、子宫内膜组织可以通过腺体和基质细胞与腹膜间皮面粘附，粘附处大部分腹膜间皮层缺损，小部分能见到完整的间皮细胞层；离体培养时间延长，间皮层逐渐缺失。
4、子宫内膜组织接种腹膜组织离体培养3d后能观察到子宫内膜基质细胞明显侵袭腹膜间皮层；内异症患者子宫内膜发生侵袭可能要早于非内异症患者子宫内膜。
5、子宫内膜组织和子宫内膜组织接种腹膜组织的培养基中sICAM-1，MMP-2和VEGF均呈活性分泌；腹膜组织表达sICAM-1，基本不表达MMP-2和VEGF。
6、内异症患者子宫内膜组织和非内异症患者子宫内膜组织存在超微结构差异，前者表现更活跃的功能结构。
7、内异症和非内异症患者子宫内膜组织与腹膜组织离体培养后粘附情况差别不大。
8、内异症患者子宫内膜组织离体培养后分泌sICAM-1较非内异症患者明显增快。
结论
1、本课题探索了子宫内膜组织的培养技术，表明子宫内膜组织置于气液界面培养，组织存活状态较好；子宫内膜组织与腹膜组织共培养于气液平面，用滤膜维持腹膜的平整牵张状态，可以提高子宫内膜组织与腹膜的粘附成功率。
2、子宫内膜接种于腹膜离体培养后粘附发生时间很早，1小时即可形成牢固粘附。子宫内膜可以通过腺体和基质细胞介导与腹膜粘附，可以和间皮层完整或不完整的腹膜粘附，并发生侵袭；随培养时间延长，粘附处腹膜间皮层逐渐缺失。
3、子宫内膜接种于腹膜离体培养3天后能见到明显的侵袭发生，主要为基质细胞介导；内异症患者子宫内膜发生侵袭可能要早于非内异症患者。
4、内异症子宫内膜组织与非内异症内膜组织的超微结构有一定差异，前者有功能活跃的特点，再一次提示在位内膜在内异症发病中的重要作用。
5、粘附是子宫内膜组织与腹膜组织相互作用的第一步，或“早期事件”，在内异症和非内异症患者间差异不显著，但这种粘附的清除以及后面的侵袭，可能在内异症和非内异症患者有所不同。
6、腹膜间皮层的缺损可能是由于内异症患者盆腹腔存在更多的细胞因子作用的结果，并促成内异症的发生。
7、作为重要的细胞粘附因子ICAM-1，在内异症在位内膜表达低，而在剪碎离体培养后其sICAM-1分泌增快，说明内异症患者在位内膜在原位易于脱离粘附，而游离于盆腹腔时易于成功粘附，为内异症发生的重要机制之一。
Establishment of a novel in vitro model—human Endometriosis histologic model and investigation of the attachment characteristic of the eutopic endometrium from endometriosis and non-endometriosis women.
Background
Endometriosis is a common disease of the reproductive women that induces menorrhalgia, chronic pelvic pain and infertility and affects their health as well as life quality. The pathogenesis has not been clearly clarified and treatment options are limited. Among the theories of endometriosis, the implantation theory of Sampson is widely accepted. However, it can't explain that up to 90％of women may experience some degree of retrograde menstruation yet only a few develop endometriosis and how endometriosis can form outside the peritoneal cavity. The latest research has revealed some differences of eutopic endometrium between endomertiosis patients and normal women, as far as the endometrial ultramicrostructure, gene, expression product of DNA and functional status are concerned.
Models are the important tool for studying endometriosis. Some kinds of endometriosis models have been established, but they have insufficiency. Such as cell models, quite different from the real physiological status in human being, are unable to reflect the comprehensive and complicated interactions of cells in vivo. Some animal models, such as rabbit model and rat model, are regarded by some scholars not suitable and lack a menstrual cycle. Ideal models of macaque or baboon are rare and too expensive so lacks of feasibility for research.
Endometriosis histo]ogic model is a novel model in recent 10 years, established by inoculation of in-vitro-separated endometrium fragments on peritoneum, It has the following advantages:①good imitation: It reflects direct interaction of endometrium and peritoneum and imitates pathogensis in early stage.②It presents a visibly dynamic and progressive development for understanding the adhesion, aggressiveness and agiogenesis of eutopic endometrium to peritonaeum and provides direct histologic proof.③suitable for comparison of endometrium and peritoneum in patients and normal women.④aboundant in resources and feasible in practice. But the suitable culture condition about the model is not found out and no research is involved in quantitation up to now.
Objective
1. To investigate culture environment for endometrium and the adhesion of endometrium to peritoneum.
2. To analyze the cellular and biomolecular features in adhesion of endometrium to peritoneum.
3. To compare the adhesion features of eutopic endometrium from patients with endometriosis and the control.
Methods
1. Observe and compare the effect on endometrium and adhesion of endometrium to peritoneum using gas-liquid surface culture and in-medium culture.
2. Collect specimens at different times for observation under light microscope and electron microscope to learn the timing of adhesion and the cellular features at adhesion sites. Detect secretion of sICAM-1, MMP-2 and VEGF in cultures using ELISA technique.
3. Identify the cells at adhesion sites using immunohiotochemistry and immunofluorescence techniques.
4. Observe and compare the endometrium as well as peritoneum from patients with endometriosis and the control under electron microscope.
5. Observe and compare the adhesion characteristic after auto inoculation and cross inoculation of endometrium to peritoneum using vibration test, light microscope and electron microscope.
6. Culture endometrium of patients with endometriosis and the control for detection of sICAM-1 secretion by ELISA.
Results
1. Gas-liquid surface culture is superior to in medium culture in maintaining tissue structure and survival.
2. Faster adhesion and invasion of endometrium to peritoneum is observed in gas-liquid surface culture.
3. Peritoneal mesothelium defects were found after adhesion by gland cells and stromal cells of endometrium and disappeared gradually as the cultivation continued.
4. Apparent invasion of endometrium into peritoneum was observed in culture 3 days after inoculation. There was a seemingly trend that the endometrium of patients with endometriosis had an earlier invasion than that of the control.
5. Active secretion of sICAM-1, MMP-2 and VEGF was detected in endometrium culture and peritoneum culture with inoculation of endometrium, sICAM-1 was expressed in peritoneum with little MMP-2 and VEGF.
6. Ultrastructural discrepancy was found between endometrium of patients with endometriosis and that of the control, the former demonstrating more active functional units.
7. There was little difference in adhesion ability in vitro between endometrium of patients with endometriosis and that of the control.
8. There was an higher increase in sICAM-1 secretion in cultured endometrium of patients with endometriosis than that of the control.
Conclusion
1. Gas-liquid surface culture is suitable for human endometriosis histologic model.
2. Adhesion of endometrium to peritoneum progresses very quickly as evidenced by formation of firm adhesion only one hour after inoculation and apparent invasion into the fibrous layer of peritoneum 3 days later.
3. Some differences were observed in the eutopic endometrial ultrastructure between endometriosis and non-endometriosis women indicating the former has an active function, with suggests eutopic endometrium plays an important role in the pathogenesis of endometriosis.
4. There was little difference in adhesion ability in vitro between endometrium of patients with endometriosis and that of the control, however, there might be some differences in the clearance of the adhesion and subsequent invision.
5. The mesothelial layer defect may be due to the multiple actions of cellular factors in the abdominal cavity.
6. The sICAM-1 levels increase significantly more quickly in cultured endometrium of patients with endometriosis than that in the control, indicating easier adhesion of endometrium fragments with little clearance.
研究背景
子宫内膜异位症(Endometriosis，简称内异症)是育龄妇女的多发病。它所引起的痛经、下腹痛和不孕严重影响妇女的健康和生活质量。目前发病机制不清，治疗对策有限。
在内异症诸多的发病学说中，Sampson的经血逆流学说是主导理论，但其难以解释经血逆流现象中仅小部分形成内异症以及盆腹腔以外内异症的问题。新近的研究提示，造成这一现象的原因是内异症的在位内膜与正常人相比，具有诸如超微结构、基因、表达产物和机能状态的差异。
模型建立是研究内异症的重要手段。尽管已成功构建了多种内异症模型，但仍然存在一些不足，如细胞模型与人体生理状况有较大差别，不能反映人体各种细胞间相互影响的错综复杂的关系；动物模型的模拟程度一直为一些学者所批评，认为内异症是人类和非人类灵长类动物(包括猕猴和狒狒等)所特有的一种疾病，而大多数动物模型所选择的啮齿类动物和兔等无周期性月经，不发生子宫内膜异位症，用其构建内异症模型并不合理。而最理想的动物模型包括猕猴和狒狒等因其来源稀缺、价格昂贵，可行性受到了很大限制。
子宫内膜异位症人体组织学模型是近10年来出现的一种新型模型。其建模方法是用人子宫内膜组织体外分离成组织碎片后接种于腹膜组织间皮面共培养以探索子宫内膜异位症的发病机制。它的优点在于：①模拟程度高：它直接反映了人体子宫内膜与人体腹膜的相互作用，模拟内异症的早期发病过程；②可动态观察内异症患者在发病早期在位内膜与腹膜组织粘附、侵袭并形成新生血管的连续过程，得到直接组织学证据；③可比较分析内异症和非内异症患者在位内膜和腹膜的异同，为进一步探索病因提供途径；④资源丰富，可行性好。但是，迄今为止，关于此模型的研究均为定性研究，且各家培养条件不一，结果差异也较大；尚未有研究涉及到定量分析。
研究目的
1、探索子宫内膜组织培养条件及子宫内膜组织与腹膜组织粘附的培养条件。
2、分析子宫内膜与腹膜粘附的细胞学行为及分子生物学表现。
3、对比研究内异症和非内异症患者子宫内膜与腹膜的粘附特点。
研究方法
1、比观察气液面培养和培养基中培养对于子宫内膜组织及子宫内膜组织粘附腹膜的影响。
2、子宫内膜接种腹膜后在培养的不同时间点收集标本用光镜观察子宫内膜与腹膜粘附发生的时间，粘附部位的细胞学行为。
3、免疫组化和免疫荧光方法鉴别粘附部位各种细胞及ELISA检测培养基中sICAM-1、MMP-2和VEGF的分泌。
4、电镜观察内异症和非内异症患者的子宫内膜组织和腹膜组织的异同。
5、振荡试验、光镜和电镜观察内异症和非内异症患者的子宫内膜与腹膜自身及交叉接种后各组间粘附的异同。
6、进行内异症和非内异症患者的子宫内膜组织培养，ELISA检测培养基中sICAM-1的分泌规律。
结果
1、子宫内膜组织气液平面培养较培养基中培养组织结构维持好，离体培养时间长。
2、子宫内膜组织和腹膜组织在气液平面培养能较早发生粘附和侵袭。
3、子宫内膜组织可以通过腺体和基质细胞与腹膜间皮面粘附，粘附处大部分腹膜间皮层缺损，小部分能见到完整的间皮细胞层；离体培养时间延长，间皮层逐渐缺失。
4、子宫内膜组织接种腹膜组织离体培养3d后能观察到子宫内膜基质细胞明显侵袭腹膜间皮层；内异症患者子宫内膜发生侵袭可能要早于非内异症患者子宫内膜。
5、子宫内膜组织和子宫内膜组织接种腹膜组织的培养基中sICAM-1，MMP-2和VEGF均呈活性分泌；腹膜组织表达sICAM-1，基本不表达MMP-2和VEGF。
6、内异症患者子宫内膜组织和非内异症患者子宫内膜组织存在超微结构差异，前者表现更活跃的功能结构。
7、内异症和非内异症患者子宫内膜组织与腹膜组织离体培养后粘附情况差别不大。
8、内异症患者子宫内膜组织离体培养后分泌sICAM-1较非内异症患者明显增快。
结论
1、本课题探索了子宫内膜组织的培养技术，表明子宫内膜组织置于气液界面培养，组织存活状态较好；子宫内膜组织与腹膜组织共培养于气液平面，用滤膜维持腹膜的平整牵张状态，可以提高子宫内膜组织与腹膜的粘附成功率。
2、子宫内膜接种于腹膜离体培养后粘附发生时间很早，1小时即可形成牢固粘附。子宫内膜可以通过腺体和基质细胞介导与腹膜粘附，可以和间皮层完整或不完整的腹膜粘附，并发生侵袭；随培养时间延长，粘附处腹膜间皮层逐渐缺失。
3、子宫内膜接种于腹膜离体培养3天后能见到明显的侵袭发生，主要为基质细胞介导；内异症患者子宫内膜发生侵袭可能要早于非内异症患者。
4、内异症子宫内膜组织与非内异症内膜组织的超微结构有一定差异，前者有功能活跃的特点，再一次提示在位内膜在内异症发病中的重要作用。
5、粘附是子宫内膜组织与腹膜组织相互作用的第一步，或“早期事件”，在内异症和非内异症患者间差异不显著，但这种粘附的清除以及后面的侵袭，可能在内异症和非内异症患者有所不同。
6、腹膜间皮层的缺损可能是由于内异症患者盆腹腔存在更多的细胞因子作用的结果，并促成内异症的发生。
7、作为重要的细胞粘附因子ICAM-1，在内异症在位内膜表达低，而在剪碎离体培养后其sICAM-1分泌增快，说明内异症患者在位内膜在原位易于脱离粘附，而游离于盆腹腔时易于成功粘附，为内异症发生的重要机制之一。
Establishment of a novel in vitro model—human Endometriosis histologic model and investigation of the attachment characteristic of the eutopic endometrium from endometriosis and non-endometriosis women.
Background
Endometriosis is a common disease of the reproductive women that induces menorrhalgia, chronic pelvic pain and infertility and affects their health as well as life quality. The pathogenesis has not been clearly clarified and treatment options are limited. Among the theories of endometriosis, the implantation theory of Sampson is widely accepted. However, it can't explain that up to 90％of women may experience some degree of retrograde menstruation yet only a few develop endometriosis and how endometriosis can form outside the peritoneal cavity. The latest research has revealed some differences of eutopic endometrium between endomertiosis patients and normal women, as far as the endometrial ultramicrostructure, gene, expression product of DNA and functional status are concerned.
Models are the important tool for studying endometriosis. Some kinds of endometriosis models have been established, but they have insufficiency. Such as cell models, quite different from the real physiological status in human being, are unable to reflect the comprehensive and complicated interactions of cells in vivo. Some animal models, such as rabbit model and rat model, are regarded by some scholars not suitable and lack a menstrual cycle. Ideal models of macaque or baboon are rare and too expensive so lacks of feasibility for research.
Endometriosis histo]ogic model is a novel model in recent 10 years, established by inoculation of in-vitro-separated endometrium fragments on peritoneum, It has the following advantages:①good imitation: It reflects direct interaction of endometrium and peritoneum and imitates pathogensis in early stage.②It presents a visibly dynamic and progressive development for understanding the adhesion, aggressiveness and agiogenesis of eutopic endometrium to peritonaeum and provides direct histologic proof.③suitable for comparison of endometrium and peritoneum in patients and normal women.④aboundant in resources and feasible in practice. But the suitable culture condition about the model is not found out and no research is involved in quantitation up to now.
Objective
1. To investigate culture environment for endometrium and the adhesion of endometrium to peritoneum.
2. To analyze the cellular and biomolecular features in adhesion of endometrium to peritoneum.
3. To compare the adhesion features of eutopic endometrium from patients with endometriosis and the control.
Methods
1. Observe and compare the effect on endometrium and adhesion of endometrium to peritoneum using gas-liquid surface culture and in-medium culture.
2. Collect specimens at different times for observation under light microscope and electron microscope to learn the timing of adhesion and the cellular features at adhesion sites. Detect secretion of sICAM-1, MMP-2 and VEGF in cultures using ELISA technique.
3. Identify the cells at adhesion sites using immunohiotochemistry and immunofluorescence techniques.
4. Observe and compare the endometrium as well as peritoneum from patients with endometriosis and the control under electron microscope.
5. Observe and compare the adhesion characteristic after auto inoculation and cross inoculation of endometrium to peritoneum using vibration test, light microscope and electron microscope.
6. Culture endometrium of patients with endometriosis and the control for detection of sICAM-1 secretion by ELISA.
Results
1. Gas-liquid surface culture is superior to in medium culture in maintaining tissue structure and survival.
2. Faster adhesion and invasion of endometrium to peritoneum is observed in gas-liquid surface culture.
3. Peritoneal mesothelium defects were found after adhesion by gland cells and stromal cells of endometrium and disappeared gradually as the cultivation continued.
4. Apparent invasion of endometrium into peritoneum was observed in culture 3 days after inoculation. There was a seemingly trend that the endometrium of patients with endometriosis had an earlier invasion than that of the control.
5. Active secretion of sICAM-1, MMP-2 and VEGF was detected in endometrium culture and peritoneum culture with inoculation of endometrium, sICAM-1 was expressed in peritoneum with little MMP-2 and VEGF.
6. Ultrastructural discrepancy was found between endometrium of patients with endometriosis and that of the control, the former demonstrating more active functional units.
7. There was little difference in adhesion ability in vitro between endometrium of patients with endometriosis and that of the control.
8. There was an higher increase in sICAM-1 secretion in cultured endometrium of patients with endometriosis than that of the control.
Conclusion
1. Gas-liquid surface culture is suitable for human endometriosis histologic model.
2. Adhesion of endometrium to peritoneum progresses very quickly as evidenced by formation of firm adhesion only one hour after inoculation and apparent invasion into the fibrous layer of peritoneum 3 days later.
3. Some differences were observed in the eutopic endometrial ultrastructure between endometriosis and non-endometriosis women indicating the former has an active function, with suggests eutopic endometrium plays an important role in the pathogenesis of endometriosis.
4. There was little difference in adhesion ability in vitro between endometrium of patients with endometriosis and that of the control, however, there might be some differences in the clearance of the adhesion and subsequent invision.
5. The mesothelial layer defect may be due to the multiple actions of cellular factors in the abdominal cavity.
6. The sICAM-1 levels increase significantly more quickly in cultured endometrium of patients with endometriosis than that in the control, indicating easier adhesion of endometrium fragments with little clearance.
引文
1 司徒镇强，吴军正．细胞培养[M]．西安：世界图书出版公司，1996．72．
2 王自能 黄丹 郑佩俄 米非司酮对体外培养人子宫内膜的损伤作用 解剖学研究 2002年第24卷第3期Anat Res，2002，Vol 24，No．3
3 谭冬梅，谭毅，赵劼等，小鼠子宫内膜的组织培养，第四军医大学学报 2005；26(7)
4 Osteen, K. G., Rodgers, W. H., Gaire, M., Hargrove, J. T., Gorstein, F., and Matrisian, L. M.. Stromal-epithelial interaction mediates steroidal regulation of metalloproteinase expression in human endometrium. Proc. 。Natl, Acad. Sci. U. S. A. 1994. 91, 10129-10133.
5 Koks CA, Dunselman GA, de Goeij AF, Arends JW, Evers JL. Evaluation of a menstrual cup to collect shed endometrium for in vitro studies. Fertil Steril. 1997 Sep; 68(3): 560-4
6 Sophie Debrock, Sarah Vander Perre, Christel Meuleman, Philippe Moerman, Joseph A. Hilll and Thomas M. D' Hooghe。In-vitro adhesion of endometrium to autologous peritoneal membranes: effect of the cycle phase and the stage of endometriosis. Human Reproduction 2002. Vol. 17, No. 10 pp. 2523-2528.
7 van der Linden PJ, de Goeij AF, Dunselman GA, Erkens HW, Evers JL. Endometrial cell adhesion in an in vitro model using intact amniotic membranes. Fertil Steril. 1996. Jan; 65(1): 76-80.
8 Groothuis PG, Koks CA, de Goeij AF, Dunselman GA, Arends JW, Evers JL. Adhesion of human endometrium to the epithelial lining and extracellular matrix of amnion in vitro: an electron microscopic study. Hum Reprod. 1998. Aug; 13(8): 2275-81
9 Groothuis PG, Koks CA, de Goeij AF, Dunselman GA, Arends JW, Evers JL. Adhesion of human endometrial fragments to peritoneum in vitro. Fertil Steril. 1999 Jun; 71(6): 1119-24.
10 Koks, C. A. M., Groothuis, P. G., Dunselman, G. A. J., De Goeij, A. F. P. M. and Evers, J. L. H. Adhesion of shed menstrual tissue in an in-vitro model using amnion and peritoneum: a light and electron micrsocopic study. Hum. Reprod. 1999, 14, 816-822.
11 Witz CA, Monotoya-Rodriguez IA, Schenken RS. Whole explants of peritoneum and endometrium: a novel model of the early endometriosis lesion. Fertil Steril. 1999 Jan; 71(1): 56-60.
12 Witz CA, Thomas MR, Montoya-Rodriguez IA, Nair AS, Centonze VE, Schenken RS. Short-term culture of peritoneum explants confirms attachment of endometrium to intact peritoneal mesothelium. Fertil Steril. 2001 Feb; 75(2): 385-90. Comment in: Fertil Steril. 2001 Aug; 76(2): 421-2. Fertil Steril. 2001 Sep; 76(3): 642-3.
13 Witz CA, Allsup KT, Montoya-Rodriguez IA, Vaughn SL, Centonze VE, Schenken RS. Culture of menstrual endometrium with peritoneal explants and mesothelial monolayers confirms attachment to intact mesothelial cells. Hum Reprod. 2002 Nov; 17(11): 2832-8.
14 D'Hooghe TM, Bambra CS, Raeymaekers BM, de Jonge I, Lauweryns JM, Koninckx PR. Intrapelvic injection of menstrual endometrium causes endomehiosis in baboons (Papio anubis and Papio c3, nocepha]us). Am J Obstet Gynecol 1995; 173: 125-34.
15 Nisolle M, Casanas-Roux F, Donnez J. Early-stage endometriosis: adhesion and growth of human menstrual endometrium in nude mice. Fertil Steril. 2000 Aug; 74(2): 306-12
16 Jonecko A. The human peritoneum and human peritonitis in ultrastructural and immunohistochemica] studies. Z Mikrosk Anat Forsch. 1990; 104(6): 907-431.
17 Leak LV. Distribution of cell surface charges on mesothelium and lymphatic endothelium. Microvasc Res 1986; 31: 18-30.
18 Zederfeldt B, Jiborn H, Blomquist P, Ude'n P. Healing of the peritoneum. In: Treutner KH, Schumpelick V, eds. Peritoneal adhesions. Berlin: Springer-Verlag, 1997: 29-34. 16. Te Linde RW, Scott RB. Experimental endometriosis. Am J Obstet Gynecol 1950; 60: 1147-73.
19 Jonecko A. The human peritoneum and human peritonitis in ultrastructural and immunohistochemical studies. Z Mikrosk Anat Forsch. 1990; 104(6): 907-43.
20 Andreoli, S. P., Mallett, C., Williams, K. et al. Mechanisms of polymorphonuclear leukocyte mediated peritoneal mesothelial cell injury. Kidney Int, 1994, 46, 1100-1109.
21 Koks CA, Demir Weusten AY, Groothuis PG, Dunselman GA, de Goeij AF, Evers JL. Menstruum induces changes in mesothelial cell morphology. Gynecol Obstet Invest. 2000: 50(1): 13-8
22 Bouvy, N. D., Marquet, R. L., Jeekel, H. and Bonier, H. J. Impact of gas(less) laparoscopy and laparotomy on peritoneal tumor growth and abdominal wall metastases. Ann. Surg. 1996, 224, 694-700.
23 Volz, J., Ko ster, S., Schaeff, B. and Paolucci, V. Laparoscopic surgery: The effects of insufflation on tumor-induced lethality in nude mice. Am. J. Obstet. Gynecol, 1998, 178, 793-795.
24 van der Linden PJ, de Goeij AF, Dunselman GA, Erkens HW, Evers JL. Amniotic membrane as an in vitro model for endometrium-extracellular matrix interactions. Gynecol Obstet Invest. 1998; 45(1): 7-11.
25 Nisolle M, Casanas-Roux F, Marbaix E, Jadoul P, Donnez J. Transplantation of cultured explants of human endometrium into nude mice. Hum. Reprod 2000; 15: 572-7. Fertil Steril 2000: 74: 306-12.
26 Annemiek W. Napl, Patrick G. Groothuis, Ayse Y. Demir, Jacques W. M. Maas, Gerard A. J. Dunselmanl, Anton F. P. M. de Goeij, and Johannes L. H. Evers, Tissue integrity is essential for ectopic implantation of human endometrium in the chicken chorioallantoic membrane。Hum. Reprod. Vol. 18, No. 1 pp. 30-34, 2003 Hum. Reprod., 14, 815-822.
27 WildRA, Zhang RJ, Medders D. Whole endometrial fragments form characteristics of in vivo endometriosis in a mesothelial cell co-culture system: an in vitro model for the study of the histogenesis of endometriosis. J Soc Gynecol Investig. 1994 Jan-Mar: 1(1): 65-8.
28 Beliard A, Noel A, Goffin F, Frankenne F, Foidart JM. Role of endocrine status and cell type in adhesion of human endometrial cells to the peritoneum in nude mice. Fertil Steril. 2002 Nov; 78(5): 973-8
29 Witz CA, Cho S, Centonze VE, Montoya-Rodriguez IA, Schenken RS. Time series analysis of transmesothelial invasion by endometrial stromal and epithelial cells using three-dimensional confocal microscopy. Fertil Steril. 2003 Mar; 79 Suppl 1: 770-8.
1 Fedele L, Marchini M, Bianchi S, et al. Structural and ultrastructural defects in preovulatory endometrium of normo-ovulating infertile women with minimal or mild endometriosis. Fertil Steril, 1990, 53: 989-993.
2 Garcia-Velasco JA, Arici A. Is the endometrium or oocyte/embryo affected in endometriosis? Hum-Reprod. 1999, 14 Suppl 2: 77-89.
3 Sharpe-Timms KL, Zimmer RL, Ricke EA, et al. Endometriotic haptoglobin binds to peritoneal macrophages and alters their function in women with endometriosis. Fertil Steril, 2002, 78: 810-819.
4 Fang Z, gang S, Gurates B, et al. Genetic or enzymatic disruption of aromatase inhibits the growth of ectopic uterine tissue. J Clin Endocrinol Metab, 2002, 87: 3460-3466.
5 Dheenadayalu K, Mak I, Gordts S, et al. Aromatase P450 messenger RNA expression in eutopic endometrium is not a specific marker for pelvic endometriosis. Fertil Steril, 2002, 78: 825-829.
6 Donnez J, Smoes P, Gillerot S, et al. Vascular endothelial growth factor (VEGF) in endometriosis. Hum Reprod, 1998, 13: 1686-1690.
7 Tan XJ, Lang JH, Liu DY, et al. Expression of vascular endothelial growth factor and thrombospondin-1 mRNA in patients with endometriosis. Fertil Steril, 2002, 78: 148-153.
8 Taylor HS, Bagot C, Kardana A, et al. HOX gene expression is altered in the endometrium of women with endometriosis. Hum Repred, 1999, 14: 1328-1331.
9 Kao LC, Tulac S, Lobo S, et al. Global gene profiling in human endometrium during the window of implantation. Endocinology, 2002, 143: 2119-2138.
10 Lundeen SG, Lebovic DI, Carver JM, et al. Differential display PCR analysis of gene expression in eutopic and ectopic endometrial tissues. Presented at the Ⅶ World Congress on Endometriosis, London, May 2000.
11 Lucidi RS, Witz CA, Chrisco M, Binkley PA, Shain SA, Schenken RS. A novel in vitro model of the early endometriotic lesion demonstrates thatattachment of endometrial cells to mesothelial cells is dependent on the source of endometrial cells. Fertil Steril. 2005 Jul; 84(1): 16-21.
12 Witz CA, Cho S, Centonze VE, Montoya-Rodriguez IA, Schenken RS. Time series analysis of transmesothelial invasion by endometrial stromal and epithelial cells using three-dimensional confocal microscopy. Fertil Steril. 2003 Mar; 79 Suppl 1: 770-8.
13 Witz CA, Allsup KT, Montoya-Rodriguez IA, Vaughn SL, Centonze VE, Scbenken RS. Culture of menstrual endometrium with peritoneal explants and mesothelial monolayers confirms attachment to intact mesothelial cells. Hum Reprod. 2002 Nov; 17(11): 2832-8.
14 Witz CA, Cho S, Montoya-Rodriguez IA, Schenken RS. The atpha(2) beta(1) and alpha(3)beta(1) integrins do not mediate attachment of endometrial cells to peritoneal mesothelium. Fertil Steril. 2002 Oct; 78(4): 796-803.
15 Witz CA, Dechaud H, Montoya-Rodriguez IA, Thomas MR, Nair AS, Centonze VE, Schenken RS. An in vitro model to study the pathogenesis of the early endometriosis lesion. Ann N Y Acad Sci. 2002 Mar; 955: 296-307; discussion 340-2, 396-406.
16 Witz CA, Thomas MR, Montoya-Rodriguez IA, Nair AS, Centonze VE, Schenken RS. Short-term culture of peritoneum explants confirms attachment of endometrium to intact peritoneal mesothelium. Fertil Steril. 2001 Feb; 75(2): 385-90.
17 Witz CA, Monotoya-Rodriguez IA, Schenken RS. Whole explants of peritoneum and endometrium: a novel model of the early endometriosis lesion. Fertil Steril. 1999 Jan; 71(1): 56-60.
18 Sophie Debrock, Sarah Vander Perre, Christel Meuleman, Philippe Moerman, Joseph A. Hilll and Thomas M. D' Hoogheo In-vitro adhesion of endometrium to autologous peritoneal membranes: effect of the cycle phase and the stage of endometriosis. Human Reproduction Vol. 17, No. 10 pp. 2523-2528, 2002。
19 Groothuis PG, Koks CA, de Goeij AF, Dunselman GA, Arends JW, Evers JL. Adhesion of human endometriat fragments to peritoneum in vitro. Fertil Steril. 1999 Jun; 71(6): 1119-24.
20 Somigliana E, Vigano P, Gaffuri B, et al. Human endometrial stromal cells as a source of intercellular adhesion molecule (ICAM)-1 molecules. Human Reprod, 1996, 11: 1190-1194.
21 Vigano P, Gaffuri B, Somigliana E, et al. Expression of intercellular adhesion molecule (ICAM)-1 mRNA and protein is enhanced in endometriosis versus endometrial stromal cells in culture. Mol Hum Reprod, 1998, 4: 1150-1156.
22 Dan I, Lebovic MD, Mueller MD, et al. Immunobiology of endometriosis. Fertil Steril, 2001, 75: 1-10 .
23 任兴斌，季海生，尹超英．子宫内膜异位症患者sICAM-1-1、sVCAM-1、sCD44V6水平变化及临床意义．山东医药，2005，45：10-12．
24 FukayaT, SugawaraJyoshida, H, etal. Intercellular adhesion molecule-1 and hepatocyte growth factor in human endometriosis original investigation and are view of literature. Gynecol Obsye Invest, 1999, 47: 11-16.
25 徐兰枝 李亚里 细胞间粘附分子-1 在子宫内膜异位症的表达及意义．中国妇产科临床杂志．2006，7(2)：113-115
26 伍俊萍，张俊慧，刘银坤，等．整和素B3和细胞内粘附分子在子宫内膜异位症在位与异位内膜组织中的表达．中华妇产科杂志，1999，34：204-206．
27 冷金花 郎景和 赵栋 刘东远．子宫内膜异位症患者血清可溶性细胞间粘附分子-1 水平的检测．中华医学杂志，2002，82(3)．
1 Giudice LC, Tazuke SI, Swiersz L. Status of current research on endometriosis. J Reprod Med, 1998, 43(3 Suppl): 252-62.
2 Sampson JA. Peritoneal endometriosis due to menstrual dissemination of endometrial tissue into the pelvic cavity. Am J Obstet Gynecol 1927. 14: 422-469.
3 Halme J, Hammond MG, Hulka JF, Raj SG, Talbert LM. Retrograde menstruation in healthy women and in patients with endometriosis. Obstet Gyneco 1984. 1 64: 151-154.
4 Oosterlynck DJ, Cornillie FJ, Waer M, Vandeputte M, Koninckx PR. Women with endometriosis show a defect in natural killer activity resulting in a decreased cytotoxicity to autologous endometrium. Fertil Steril 1991. 56: 45-51.
5 Bergqvist A, Jeppsson S, Kullander S, et al. Human uterine en2 dometrium and endometriotic tissue transplanted into nude mice: morphologic effects of various steroid hormones. Am J Pathol, 1985, 121 (2): 337
6 杨耀芳，王钦茂，方学明，等．建立大鼠子宫内膜异位症模型的评价方法．中国药理学通报，1998，14(5)：469
7 Vernon MW, Wilson EA. Studies on the surgical induction of endometriosis in the rat. Fertil Steril 1985. 44: 684-694.
8 Zamah NM, Dodson MG, Stephens LC, Buttram VC, Besch PK, Kaufman RH. Transplantation of normal and ectopic human endometrial tissue into athymic nude mice. Am J Obstet Gynecol. 1984. 149: 591-597.
9 Beliard A, Noe"l A, Goffin F, Frankenne F, Foidart J. Role of endocrine status and cell type in adhesion of human endometrial cells to the peritoneum in nude mice. Fertil Steril 2002. 78: 973-978.
10 Nisolle M, Casanas-Roux F, Marbaix E, Jadoul P, Donnez J. Transplantation of cultured explants of human endometfium into nude mice. Hum Reprod 2000. 15: 572-577.
11 Nisolle M, Casanas-Roux F, Donnez J. Early-stage endometriosis: Adhesion and growth of human menstrual endometrium in nude mice. Fertil Stefil 2000. 74: 306-312.
12 Uchiide I, Ihara T, Sugamata M. Pathological evaluation of the rat endometriosis model. Fertil Steril 2002. 78: 782-786.
13 D' Hooghe TM. Clinical relevance of the baboon as a model for the study of endometriosis [J]. Fertil Steril, 1997, 68: 613-625.
14 D'Hooghe TM, Bambra CS, Suleman MA, Dunselman GA, Evers HL, Koninckx PR. Development of a model of retrograde menstruation in baboons (Papio anubis). Fertil Steril1994. 62: 635-638.
15 D'Hooghe TM, Bambra CS, Raeymaekers BM, Koninckx PR. Serial laparoscopies over 30 months show that endometriosis in captive baboons (Papio anubis, Papio cynocephalus) is a progressive disease. Fertil Steril 1996. 65: 645-649.
16 D'Hooghe TM, Bambra CS, Raeymaekers BM, De Jonge I, Hill JA, Koninckx PR. The effects of immunosuppression on development and progression of endometriosis in baboons (Papio anubis). Fertil Steril.1995. 64: 172-178.
17 Vernon MW. Experimental endometriosis in laboratory animal as a research mode. Prog Clin Biol Res, 1990, 323: 49-60
18 Fazleabas AT, Brudney A, Gurates B, et al. A modified baboon model for endometriosis. Ann N Y Acad Sci, 2002, 955: 308-17
19 D' Hooghe TM, Bambra CS, De Jonge I, et al. A serial section study of visually normal posterior pelvic peritoneum from ba2 boons with and without spontaneous endometriosis. Feril Steril, 1995, 63: 1322-1325
20 Beliard A, Noel A, Goffin F, Frankenne F, Foidart JM. Role of endocrine status and cell type in adhesion of human endometrial cells to the peritoneum in nude mice. Fertil Steril. 2002 Nov; 78(5): 973-8.
21 Witz CA, Cho S, Centonze VE, Montoya-Rodriguez IA, Schenken RS. Time series analysis of transmesothelial invasion by endometrial stromal and epithelial cells using three-dimensional confocal microscopy. Fertil Steril. 2003 Mar; 79 Suppl 1: 770-8.
22 Sharpe KL, Zimmer RL, Khan RS, Penney LL. Proliferative and morphogenic changes induced by the coculture of rat uterine and peritoneal cells: a cell culture model for endometfiosis. Fertil Steril. 1992 Dec; 58(6): 1220-9.
23 Yamauchi N, Yamada O, Takahashi T, Imai K, Sato T, Ito A, Hashizume K. A three-dimensional cell culture model for bovine endometrium: regeneration of a multicellular spheroid using ascorbate. Placenta. 2003 Feb-Mar; 24(2-3): 258-69.
24 Bentin-Ley U, Pedersen B, Lindenberg S, Larsen JF, Harnberger L, Horn T. lsolation and culture of human endometrial cells in a three-dimensional culture system. J Reprod Fertil. 1994 Jul; 101(2): 327-32.
25 Yang H, Han S, Kim H, Choi YM, Hwang KJ, Kwo HC, Kim SK, Cho DJ Expression of integrins, cyclooxygenases and matrix metalloproteinases in three-dimensional human endometrial cell culture system. Exp Mol Med. 2002 Mar 31; 34(1): 75-82.
26 Park DW, Choi DS, Ryu HS, Kwon HC, Joo H, Min CK. A well-defined in vitro three-dimensional culture of human endometrium and its applicability to endometrial cancer invasion. Cancer Lett. 2003 Jun 10; 195(2): 185-92.
27 Osteen, K. G., Rodgers, W. H., Gaire, M., Hargrove, J. T., Gorstein, F., and Matrisian, L. M. Stromal-epithelial interaction mediates steroidal regulation of metalloproteinase expression in human endometrium. Proc. Natl. Acad. Sci. U. S. A. 1994. 91, 10129-10133.
28 Alessandro Fasciani, M. D, Guido Bocci, M. D, Jing Xu, M. D., Ph. D, Ryszard Bielecki, D. V. M, Ellen Greenblatt, M. D, Nicholas Leyland, M. D, and Robert F. Casper, M. D,。 Three-dimensional in vitro culture of endometrial explants mimics the early stages of endometriosis. Fertil Steril. 2003. 80(5), 1137-1143.
29 Koks CA, Dunselman GA, de Goeij AF, Arends JW, Evers JL. Evaluation of a menstrual cup to collect shed endometrium for in vitro studies. Fertil Steril. 1997 Sep; 68(3): 560-4
30 Wild RA, Zhang RJ, Medders D. Whole endometrial fragments form characteristics of in vivo endometriosis in a mesothelial cell co-culture system: an in vitro model for the study of the histogenesis of endometriosis. J Soc Gynecol Investig. 1994 Jan-Mar; 1(1): 65-8.
31 van der Linden PJ, de Goeij AF, Dunselman GA, Erkens HW, Evers JL. Endometrial cell adhesion in an in vitro model using intact amniotic membranes. Fertil Steril. 1996 Jan; 65(1): 76-80.
32 Groothuis PG, Koks CA, de Goeij AF, Dunselman GA, Arends JW, Evers JL. Adhesion of human endometrium to the epithelial lining and extracellular matrix of amnion in vitro: an electron microscopic study. Hum Reprod. 1998 Aug; 13(8): 2275-81. Groothuis PG, Koks CA, de Goeij AF, Dunselman GA, Arends JW, Evers JL. Adhesion of human endometrial fragments to peritoneum in vitro. Fertil Steril. 1999 Jun; 71(6): 1119-24.
33 Koks CA, Demir Weusten AY, Groothuis PG, Dunselman GA, de Goeij AF, Evers JL. Menstruum induces changes in mesothelial cell morphology. Gynecol Obstet Invest. 2000; 50(1): 13-8.
34 Debrock S, Vander Perre S, Meuleman C, Moerman P, Hill JA, D'Hooghe TM. In-vitro adhesion of endometrium to autologous peritoneal membranes: effect of the cycle phase and the stage of endometriosis. Hum Reprod. 2002 Oct; 17(10): 2523-8.
35 Witz CA, Monotoya-Rodriguez IA, Schenken RS. Whole explants of peritoneum and endometrium: a novel model of the early endometriosis lesion. Fertil Steril. 1999 Jan; 71(1): 56-60.
36 Witz CA, Dechaud H, Montoya-Rodriguez IA, Thomas MR, Nair AS, Centonze VE, Schenken RS. An in vitro model to study the pathogenesis of the early endometriosis lesion. Ann N Y Acad Sci. 2002 Mar; 955: 296-307; discussion 340-2, 396-406.
37 Witz CA, Allsup KT, Montoya-Rodriguez IA, Vaughn SL, Centonze VE, Schenken RS. Culture of menstrual endometrium with peritoneal explants and mesothelial monolayers confirms attachment to intact mesothelial cells. Hum Reprod. 2002 Nov; 17(11) :2832-8.。
38 Witz CA Witz CA, Allsup KT, Montoya-Rodriguez IA, Vaughan SL, Centonze VE, Schenken RS. Pathogenesis of endometriosis--current research. Hum Fertil (Camb). 2003 Feb; 6(1): 34-40.
39 Dechaud H, Witz CA, Montoya-Rodriguez IA, Degraffenreid LA, Schenken RS. Mesothelial cell-associated hyaluronic acid promotes adhesion of endometrial ceils to mesothelium. Fertil Steril. 2001 Nov; 76(5): 1012-8.
40 Witz CA, Cho S, Montoya-Rodriguez IA, Schenken RS. The alpha(2)beta(1) and alpha(3)beta(1) integrins do not mediate attachment of endometrial cells to peritoneal mesothelium. Fertil Steril. 2002 Oct; 78(4): 796-803.
41 Jacques W.M.Maas, Patrick G.Groothuis, Gerard A.J.Dunselman, Development of endometriosis-like lesions after transplantation of human endometrial fragments onto the chick embryo chorioallantoic membrane Human Repro Vol. 2001.16, No.4 pp. 627-631,。
42 Annemiek W.Nap, Patrick G.Groothuis, Ayse Y.Demir, Jacques W.M.Maas, Gerard A.J.Dunselman, Anton F.P.M.de Goeij, and Johannes L.H.Evers. Tissue integrity is essential for ectopic implantation of human endometrium in the chicken chorioallantoic membrane。Hum.Reprod., Vol.18, No.1 pp. 30-34, 2003 Hum.Reprod., 14, 816-822.
43 Nap AW, Dunselman GA, Griffioen AW, Mayo KH, Evers JL, Groothuis PG. Angiostatic agents prevent the development of endometriosis-like lesions in the chicken chorioallantoic membrane. Fertil Steril. 2005 Mar; 83(3): 793-5.
44 Nap AW, Dunselman GA, de Goeij AF, Evers JL, Groothuis PG. Inhibiting MMP activity prevents the development of endometriosis in the chicken chorioallantoic membrane model. Hum Reprod. 2004 Oct; 19(10): 2180-7. Epub 2004 Jul 8.
2 王自能 黄丹 郑佩俄 米非司酮对体外培养人子宫内膜的损伤作用 解剖学研究 2002年第24卷第3期Anat Res，2002，Vol 24，No．3
3 谭冬梅，谭毅，赵劼等，小鼠子宫内膜的组织培养，第四军医大学学报 2005；26(7)
4 Osteen, K. G., Rodgers, W. H., Gaire, M., Hargrove, J. T., Gorstein, F., and Matrisian, L. M.. Stromal-epithelial interaction mediates steroidal regulation of metalloproteinase expression in human endometrium. Proc. 。Natl, Acad. Sci. U. S. A. 1994. 91, 10129-10133.
5 Koks CA, Dunselman GA, de Goeij AF, Arends JW, Evers JL. Evaluation of a menstrual cup to collect shed endometrium for in vitro studies. Fertil Steril. 1997 Sep; 68(3): 560-4
6 Sophie Debrock, Sarah Vander Perre, Christel Meuleman, Philippe Moerman, Joseph A. Hilll and Thomas M. D' Hooghe。In-vitro adhesion of endometrium to autologous peritoneal membranes: effect of the cycle phase and the stage of endometriosis. Human Reproduction 2002. Vol. 17, No. 10 pp. 2523-2528.
7 van der Linden PJ, de Goeij AF, Dunselman GA, Erkens HW, Evers JL. Endometrial cell adhesion in an in vitro model using intact amniotic membranes. Fertil Steril. 1996. Jan; 65(1): 76-80.
8 Groothuis PG, Koks CA, de Goeij AF, Dunselman GA, Arends JW, Evers JL. Adhesion of human endometrium to the epithelial lining and extracellular matrix of amnion in vitro: an electron microscopic study. Hum Reprod. 1998. Aug; 13(8): 2275-81
9 Groothuis PG, Koks CA, de Goeij AF, Dunselman GA, Arends JW, Evers JL. Adhesion of human endometrial fragments to peritoneum in vitro. Fertil Steril. 1999 Jun; 71(6): 1119-24.
10 Koks, C. A. M., Groothuis, P. G., Dunselman, G. A. J., De Goeij, A. F. P. M. and Evers, J. L. H. Adhesion of shed menstrual tissue in an in-vitro model using amnion and peritoneum: a light and electron micrsocopic study. Hum. Reprod. 1999, 14, 816-822.
11 Witz CA, Monotoya-Rodriguez IA, Schenken RS. Whole explants of peritoneum and endometrium: a novel model of the early endometriosis lesion. Fertil Steril. 1999 Jan; 71(1): 56-60.
12 Witz CA, Thomas MR, Montoya-Rodriguez IA, Nair AS, Centonze VE, Schenken RS. Short-term culture of peritoneum explants confirms attachment of endometrium to intact peritoneal mesothelium. Fertil Steril. 2001 Feb; 75(2): 385-90. Comment in: Fertil Steril. 2001 Aug; 76(2): 421-2. Fertil Steril. 2001 Sep; 76(3): 642-3.
13 Witz CA, Allsup KT, Montoya-Rodriguez IA, Vaughn SL, Centonze VE, Schenken RS. Culture of menstrual endometrium with peritoneal explants and mesothelial monolayers confirms attachment to intact mesothelial cells. Hum Reprod. 2002 Nov; 17(11): 2832-8.
14 D'Hooghe TM, Bambra CS, Raeymaekers BM, de Jonge I, Lauweryns JM, Koninckx PR. Intrapelvic injection of menstrual endometrium causes endomehiosis in baboons (Papio anubis and Papio c3, nocepha]us). Am J Obstet Gynecol 1995; 173: 125-34.
15 Nisolle M, Casanas-Roux F, Donnez J. Early-stage endometriosis: adhesion and growth of human menstrual endometrium in nude mice. Fertil Steril. 2000 Aug; 74(2): 306-12
16 Jonecko A. The human peritoneum and human peritonitis in ultrastructural and immunohistochemica] studies. Z Mikrosk Anat Forsch. 1990; 104(6): 907-431.
17 Leak LV. Distribution of cell surface charges on mesothelium and lymphatic endothelium. Microvasc Res 1986; 31: 18-30.
18 Zederfeldt B, Jiborn H, Blomquist P, Ude'n P. Healing of the peritoneum. In: Treutner KH, Schumpelick V, eds. Peritoneal adhesions. Berlin: Springer-Verlag, 1997: 29-34. 16. Te Linde RW, Scott RB. Experimental endometriosis. Am J Obstet Gynecol 1950; 60: 1147-73.
19 Jonecko A. The human peritoneum and human peritonitis in ultrastructural and immunohistochemical studies. Z Mikrosk Anat Forsch. 1990; 104(6): 907-43.
20 Andreoli, S. P., Mallett, C., Williams, K. et al. Mechanisms of polymorphonuclear leukocyte mediated peritoneal mesothelial cell injury. Kidney Int, 1994, 46, 1100-1109.
21 Koks CA, Demir Weusten AY, Groothuis PG, Dunselman GA, de Goeij AF, Evers JL. Menstruum induces changes in mesothelial cell morphology. Gynecol Obstet Invest. 2000: 50(1): 13-8
22 Bouvy, N. D., Marquet, R. L., Jeekel, H. and Bonier, H. J. Impact of gas(less) laparoscopy and laparotomy on peritoneal tumor growth and abdominal wall metastases. Ann. Surg. 1996, 224, 694-700.
23 Volz, J., Ko ster, S., Schaeff, B. and Paolucci, V. Laparoscopic surgery: The effects of insufflation on tumor-induced lethality in nude mice. Am. J. Obstet. Gynecol, 1998, 178, 793-795.
24 van der Linden PJ, de Goeij AF, Dunselman GA, Erkens HW, Evers JL. Amniotic membrane as an in vitro model for endometrium-extracellular matrix interactions. Gynecol Obstet Invest. 1998; 45(1): 7-11.
25 Nisolle M, Casanas-Roux F, Marbaix E, Jadoul P, Donnez J. Transplantation of cultured explants of human endometrium into nude mice. Hum. Reprod 2000; 15: 572-7. Fertil Steril 2000: 74: 306-12.
26 Annemiek W. Napl, Patrick G. Groothuis, Ayse Y. Demir, Jacques W. M. Maas, Gerard A. J. Dunselmanl, Anton F. P. M. de Goeij, and Johannes L. H. Evers, Tissue integrity is essential for ectopic implantation of human endometrium in the chicken chorioallantoic membrane。Hum. Reprod. Vol. 18, No. 1 pp. 30-34, 2003 Hum. Reprod., 14, 815-822.
27 WildRA, Zhang RJ, Medders D. Whole endometrial fragments form characteristics of in vivo endometriosis in a mesothelial cell co-culture system: an in vitro model for the study of the histogenesis of endometriosis. J Soc Gynecol Investig. 1994 Jan-Mar: 1(1): 65-8.
28 Beliard A, Noel A, Goffin F, Frankenne F, Foidart JM. Role of endocrine status and cell type in adhesion of human endometrial cells to the peritoneum in nude mice. Fertil Steril. 2002 Nov; 78(5): 973-8
29 Witz CA, Cho S, Centonze VE, Montoya-Rodriguez IA, Schenken RS. Time series analysis of transmesothelial invasion by endometrial stromal and epithelial cells using three-dimensional confocal microscopy. Fertil Steril. 2003 Mar; 79 Suppl 1: 770-8.
1 Fedele L, Marchini M, Bianchi S, et al. Structural and ultrastructural defects in preovulatory endometrium of normo-ovulating infertile women with minimal or mild endometriosis. Fertil Steril, 1990, 53: 989-993.
2 Garcia-Velasco JA, Arici A. Is the endometrium or oocyte/embryo affected in endometriosis? Hum-Reprod. 1999, 14 Suppl 2: 77-89.
3 Sharpe-Timms KL, Zimmer RL, Ricke EA, et al. Endometriotic haptoglobin binds to peritoneal macrophages and alters their function in women with endometriosis. Fertil Steril, 2002, 78: 810-819.
4 Fang Z, gang S, Gurates B, et al. Genetic or enzymatic disruption of aromatase inhibits the growth of ectopic uterine tissue. J Clin Endocrinol Metab, 2002, 87: 3460-3466.
5 Dheenadayalu K, Mak I, Gordts S, et al. Aromatase P450 messenger RNA expression in eutopic endometrium is not a specific marker for pelvic endometriosis. Fertil Steril, 2002, 78: 825-829.
6 Donnez J, Smoes P, Gillerot S, et al. Vascular endothelial growth factor (VEGF) in endometriosis. Hum Reprod, 1998, 13: 1686-1690.
7 Tan XJ, Lang JH, Liu DY, et al. Expression of vascular endothelial growth factor and thrombospondin-1 mRNA in patients with endometriosis. Fertil Steril, 2002, 78: 148-153.
8 Taylor HS, Bagot C, Kardana A, et al. HOX gene expression is altered in the endometrium of women with endometriosis. Hum Repred, 1999, 14: 1328-1331.
9 Kao LC, Tulac S, Lobo S, et al. Global gene profiling in human endometrium during the window of implantation. Endocinology, 2002, 143: 2119-2138.
10 Lundeen SG, Lebovic DI, Carver JM, et al. Differential display PCR analysis of gene expression in eutopic and ectopic endometrial tissues. Presented at the Ⅶ World Congress on Endometriosis, London, May 2000.
11 Lucidi RS, Witz CA, Chrisco M, Binkley PA, Shain SA, Schenken RS. A novel in vitro model of the early endometriotic lesion demonstrates thatattachment of endometrial cells to mesothelial cells is dependent on the source of endometrial cells. Fertil Steril. 2005 Jul; 84(1): 16-21.
12 Witz CA, Cho S, Centonze VE, Montoya-Rodriguez IA, Schenken RS. Time series analysis of transmesothelial invasion by endometrial stromal and epithelial cells using three-dimensional confocal microscopy. Fertil Steril. 2003 Mar; 79 Suppl 1: 770-8.
13 Witz CA, Allsup KT, Montoya-Rodriguez IA, Vaughn SL, Centonze VE, Scbenken RS. Culture of menstrual endometrium with peritoneal explants and mesothelial monolayers confirms attachment to intact mesothelial cells. Hum Reprod. 2002 Nov; 17(11): 2832-8.
14 Witz CA, Cho S, Montoya-Rodriguez IA, Schenken RS. The atpha(2) beta(1) and alpha(3)beta(1) integrins do not mediate attachment of endometrial cells to peritoneal mesothelium. Fertil Steril. 2002 Oct; 78(4): 796-803.
15 Witz CA, Dechaud H, Montoya-Rodriguez IA, Thomas MR, Nair AS, Centonze VE, Schenken RS. An in vitro model to study the pathogenesis of the early endometriosis lesion. Ann N Y Acad Sci. 2002 Mar; 955: 296-307; discussion 340-2, 396-406.
16 Witz CA, Thomas MR, Montoya-Rodriguez IA, Nair AS, Centonze VE, Schenken RS. Short-term culture of peritoneum explants confirms attachment of endometrium to intact peritoneal mesothelium. Fertil Steril. 2001 Feb; 75(2): 385-90.
17 Witz CA, Monotoya-Rodriguez IA, Schenken RS. Whole explants of peritoneum and endometrium: a novel model of the early endometriosis lesion. Fertil Steril. 1999 Jan; 71(1): 56-60.
18 Sophie Debrock, Sarah Vander Perre, Christel Meuleman, Philippe Moerman, Joseph A. Hilll and Thomas M. D' Hoogheo In-vitro adhesion of endometrium to autologous peritoneal membranes: effect of the cycle phase and the stage of endometriosis. Human Reproduction Vol. 17, No. 10 pp. 2523-2528, 2002。
19 Groothuis PG, Koks CA, de Goeij AF, Dunselman GA, Arends JW, Evers JL. Adhesion of human endometriat fragments to peritoneum in vitro. Fertil Steril. 1999 Jun; 71(6): 1119-24.
20 Somigliana E, Vigano P, Gaffuri B, et al. Human endometrial stromal cells as a source of intercellular adhesion molecule (ICAM)-1 molecules. Human Reprod, 1996, 11: 1190-1194.
21 Vigano P, Gaffuri B, Somigliana E, et al. Expression of intercellular adhesion molecule (ICAM)-1 mRNA and protein is enhanced in endometriosis versus endometrial stromal cells in culture. Mol Hum Reprod, 1998, 4: 1150-1156.
22 Dan I, Lebovic MD, Mueller MD, et al. Immunobiology of endometriosis. Fertil Steril, 2001, 75: 1-10 .
23 任兴斌，季海生，尹超英．子宫内膜异位症患者sICAM-1-1、sVCAM-1、sCD44V6水平变化及临床意义．山东医药，2005，45：10-12．
24 FukayaT, SugawaraJyoshida, H, etal. Intercellular adhesion molecule-1 and hepatocyte growth factor in human endometriosis original investigation and are view of literature. Gynecol Obsye Invest, 1999, 47: 11-16.
25 徐兰枝 李亚里 细胞间粘附分子-1 在子宫内膜异位症的表达及意义．中国妇产科临床杂志．2006，7(2)：113-115
26 伍俊萍，张俊慧，刘银坤，等．整和素B3和细胞内粘附分子在子宫内膜异位症在位与异位内膜组织中的表达．中华妇产科杂志，1999，34：204-206．
27 冷金花 郎景和 赵栋 刘东远．子宫内膜异位症患者血清可溶性细胞间粘附分子-1 水平的检测．中华医学杂志，2002，82(3)．
1 Giudice LC, Tazuke SI, Swiersz L. Status of current research on endometriosis. J Reprod Med, 1998, 43(3 Suppl): 252-62.
2 Sampson JA. Peritoneal endometriosis due to menstrual dissemination of endometrial tissue into the pelvic cavity. Am J Obstet Gynecol 1927. 14: 422-469.
3 Halme J, Hammond MG, Hulka JF, Raj SG, Talbert LM. Retrograde menstruation in healthy women and in patients with endometriosis. Obstet Gyneco 1984. 1 64: 151-154.
4 Oosterlynck DJ, Cornillie FJ, Waer M, Vandeputte M, Koninckx PR. Women with endometriosis show a defect in natural killer activity resulting in a decreased cytotoxicity to autologous endometrium. Fertil Steril 1991. 56: 45-51.
5 Bergqvist A, Jeppsson S, Kullander S, et al. Human uterine en2 dometrium and endometriotic tissue transplanted into nude mice: morphologic effects of various steroid hormones. Am J Pathol, 1985, 121 (2): 337
6 杨耀芳，王钦茂，方学明，等．建立大鼠子宫内膜异位症模型的评价方法．中国药理学通报，1998，14(5)：469
7 Vernon MW, Wilson EA. Studies on the surgical induction of endometriosis in the rat. Fertil Steril 1985. 44: 684-694.
8 Zamah NM, Dodson MG, Stephens LC, Buttram VC, Besch PK, Kaufman RH. Transplantation of normal and ectopic human endometrial tissue into athymic nude mice. Am J Obstet Gynecol. 1984. 149: 591-597.
9 Beliard A, Noe"l A, Goffin F, Frankenne F, Foidart J. Role of endocrine status and cell type in adhesion of human endometrial cells to the peritoneum in nude mice. Fertil Steril 2002. 78: 973-978.
10 Nisolle M, Casanas-Roux F, Marbaix E, Jadoul P, Donnez J. Transplantation of cultured explants of human endometfium into nude mice. Hum Reprod 2000. 15: 572-577.
11 Nisolle M, Casanas-Roux F, Donnez J. Early-stage endometriosis: Adhesion and growth of human menstrual endometrium in nude mice. Fertil Stefil 2000. 74: 306-312.
12 Uchiide I, Ihara T, Sugamata M. Pathological evaluation of the rat endometriosis model. Fertil Steril 2002. 78: 782-786.
13 D' Hooghe TM. Clinical relevance of the baboon as a model for the study of endometriosis [J]. Fertil Steril, 1997, 68: 613-625.
14 D'Hooghe TM, Bambra CS, Suleman MA, Dunselman GA, Evers HL, Koninckx PR. Development of a model of retrograde menstruation in baboons (Papio anubis). Fertil Steril1994. 62: 635-638.
15 D'Hooghe TM, Bambra CS, Raeymaekers BM, Koninckx PR. Serial laparoscopies over 30 months show that endometriosis in captive baboons (Papio anubis, Papio cynocephalus) is a progressive disease. Fertil Steril 1996. 65: 645-649.
16 D'Hooghe TM, Bambra CS, Raeymaekers BM, De Jonge I, Hill JA, Koninckx PR. The effects of immunosuppression on development and progression of endometriosis in baboons (Papio anubis). Fertil Steril.1995. 64: 172-178.
17 Vernon MW. Experimental endometriosis in laboratory animal as a research mode. Prog Clin Biol Res, 1990, 323: 49-60
18 Fazleabas AT, Brudney A, Gurates B, et al. A modified baboon model for endometriosis. Ann N Y Acad Sci, 2002, 955: 308-17
19 D' Hooghe TM, Bambra CS, De Jonge I, et al. A serial section study of visually normal posterior pelvic peritoneum from ba2 boons with and without spontaneous endometriosis. Feril Steril, 1995, 63: 1322-1325
20 Beliard A, Noel A, Goffin F, Frankenne F, Foidart JM. Role of endocrine status and cell type in adhesion of human endometrial cells to the peritoneum in nude mice. Fertil Steril. 2002 Nov; 78(5): 973-8.
21 Witz CA, Cho S, Centonze VE, Montoya-Rodriguez IA, Schenken RS. Time series analysis of transmesothelial invasion by endometrial stromal and epithelial cells using three-dimensional confocal microscopy. Fertil Steril. 2003 Mar; 79 Suppl 1: 770-8.
22 Sharpe KL, Zimmer RL, Khan RS, Penney LL. Proliferative and morphogenic changes induced by the coculture of rat uterine and peritoneal cells: a cell culture model for endometfiosis. Fertil Steril. 1992 Dec; 58(6): 1220-9.
23 Yamauchi N, Yamada O, Takahashi T, Imai K, Sato T, Ito A, Hashizume K. A three-dimensional cell culture model for bovine endometrium: regeneration of a multicellular spheroid using ascorbate. Placenta. 2003 Feb-Mar; 24(2-3): 258-69.
24 Bentin-Ley U, Pedersen B, Lindenberg S, Larsen JF, Harnberger L, Horn T. lsolation and culture of human endometrial cells in a three-dimensional culture system. J Reprod Fertil. 1994 Jul; 101(2): 327-32.
25 Yang H, Han S, Kim H, Choi YM, Hwang KJ, Kwo HC, Kim SK, Cho DJ Expression of integrins, cyclooxygenases and matrix metalloproteinases in three-dimensional human endometrial cell culture system. Exp Mol Med. 2002 Mar 31; 34(1): 75-82.
26 Park DW, Choi DS, Ryu HS, Kwon HC, Joo H, Min CK. A well-defined in vitro three-dimensional culture of human endometrium and its applicability to endometrial cancer invasion. Cancer Lett. 2003 Jun 10; 195(2): 185-92.
27 Osteen, K. G., Rodgers, W. H., Gaire, M., Hargrove, J. T., Gorstein, F., and Matrisian, L. M. Stromal-epithelial interaction mediates steroidal regulation of metalloproteinase expression in human endometrium. Proc. Natl. Acad. Sci. U. S. A. 1994. 91, 10129-10133.
28 Alessandro Fasciani, M. D, Guido Bocci, M. D, Jing Xu, M. D., Ph. D, Ryszard Bielecki, D. V. M, Ellen Greenblatt, M. D, Nicholas Leyland, M. D, and Robert F. Casper, M. D,。 Three-dimensional in vitro culture of endometrial explants mimics the early stages of endometriosis. Fertil Steril. 2003. 80(5), 1137-1143.
29 Koks CA, Dunselman GA, de Goeij AF, Arends JW, Evers JL. Evaluation of a menstrual cup to collect shed endometrium for in vitro studies. Fertil Steril. 1997 Sep; 68(3): 560-4
30 Wild RA, Zhang RJ, Medders D. Whole endometrial fragments form characteristics of in vivo endometriosis in a mesothelial cell co-culture system: an in vitro model for the study of the histogenesis of endometriosis. J Soc Gynecol Investig. 1994 Jan-Mar; 1(1): 65-8.
31 van der Linden PJ, de Goeij AF, Dunselman GA, Erkens HW, Evers JL. Endometrial cell adhesion in an in vitro model using intact amniotic membranes. Fertil Steril. 1996 Jan; 65(1): 76-80.
32 Groothuis PG, Koks CA, de Goeij AF, Dunselman GA, Arends JW, Evers JL. Adhesion of human endometrium to the epithelial lining and extracellular matrix of amnion in vitro: an electron microscopic study. Hum Reprod. 1998 Aug; 13(8): 2275-81. Groothuis PG, Koks CA, de Goeij AF, Dunselman GA, Arends JW, Evers JL. Adhesion of human endometrial fragments to peritoneum in vitro. Fertil Steril. 1999 Jun; 71(6): 1119-24.
33 Koks CA, Demir Weusten AY, Groothuis PG, Dunselman GA, de Goeij AF, Evers JL. Menstruum induces changes in mesothelial cell morphology. Gynecol Obstet Invest. 2000; 50(1): 13-8.
34 Debrock S, Vander Perre S, Meuleman C, Moerman P, Hill JA, D'Hooghe TM. In-vitro adhesion of endometrium to autologous peritoneal membranes: effect of the cycle phase and the stage of endometriosis. Hum Reprod. 2002 Oct; 17(10): 2523-8.
35 Witz CA, Monotoya-Rodriguez IA, Schenken RS. Whole explants of peritoneum and endometrium: a novel model of the early endometriosis lesion. Fertil Steril. 1999 Jan; 71(1): 56-60.
36 Witz CA, Dechaud H, Montoya-Rodriguez IA, Thomas MR, Nair AS, Centonze VE, Schenken RS. An in vitro model to study the pathogenesis of the early endometriosis lesion. Ann N Y Acad Sci. 2002 Mar; 955: 296-307; discussion 340-2, 396-406.
37 Witz CA, Allsup KT, Montoya-Rodriguez IA, Vaughn SL, Centonze VE, Schenken RS. Culture of menstrual endometrium with peritoneal explants and mesothelial monolayers confirms attachment to intact mesothelial cells. Hum Reprod. 2002 Nov; 17(11) :2832-8.。
38 Witz CA Witz CA, Allsup KT, Montoya-Rodriguez IA, Vaughan SL, Centonze VE, Schenken RS. Pathogenesis of endometriosis--current research. Hum Fertil (Camb). 2003 Feb; 6(1): 34-40.
39 Dechaud H, Witz CA, Montoya-Rodriguez IA, Degraffenreid LA, Schenken RS. Mesothelial cell-associated hyaluronic acid promotes adhesion of endometrial ceils to mesothelium. Fertil Steril. 2001 Nov; 76(5): 1012-8.
40 Witz CA, Cho S, Montoya-Rodriguez IA, Schenken RS. The alpha(2)beta(1) and alpha(3)beta(1) integrins do not mediate attachment of endometrial cells to peritoneal mesothelium. Fertil Steril. 2002 Oct; 78(4): 796-803.
41 Jacques W.M.Maas, Patrick G.Groothuis, Gerard A.J.Dunselman, Development of endometriosis-like lesions after transplantation of human endometrial fragments onto the chick embryo chorioallantoic membrane Human Repro Vol. 2001.16, No.4 pp. 627-631,。
42 Annemiek W.Nap, Patrick G.Groothuis, Ayse Y.Demir, Jacques W.M.Maas, Gerard A.J.Dunselman, Anton F.P.M.de Goeij, and Johannes L.H.Evers. Tissue integrity is essential for ectopic implantation of human endometrium in the chicken chorioallantoic membrane。Hum.Reprod., Vol.18, No.1 pp. 30-34, 2003 Hum.Reprod., 14, 816-822.
43 Nap AW, Dunselman GA, Griffioen AW, Mayo KH, Evers JL, Groothuis PG. Angiostatic agents prevent the development of endometriosis-like lesions in the chicken chorioallantoic membrane. Fertil Steril. 2005 Mar; 83(3): 793-5.
44 Nap AW, Dunselman GA, de Goeij AF, Evers JL, Groothuis PG. Inhibiting MMP activity prevents the development of endometriosis in the chicken chorioallantoic membrane model. Hum Reprod. 2004 Oct; 19(10): 2180-7. Epub 2004 Jul 8.