1 Research Institute Growth and Development (GROW), Maastricht University, 2 Department of Obstetrics and Gynaecology and 3 Department of Pathology, Academisch Ziekenhuis Maastricht and Maastricht University, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands
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Abstract |
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Key words: adhesion/endometriosis/menstrual endometrium/meso-thelium/pathogenesis
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Introduction |
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Be this as it may, finding vital endometrial tissue in the abdominal cavity on the one hand and early lesions of peritoneal endometriosis on the other hand, does not give us much insight into the events that take place during the transition of endometrial tissue into endometriotic tissue. In other words, what happens at the encounter interface between the cells of the endometrial tissue and the peritoneal lining? Which cell types, the regurgitated endometrial epithelial glandular tissue or the stromal tissue, single cells or tissue fragments, are making the first contact with the mesothelial cells of the peritoneum? Or, alternatively, does the endometrium make direct contact with the submesothelial extracellular matrix, and if so, how does it pass through the mesothelial lining?
Does the mesothelium act as a barrier for the endometrium or is it receptive: Teflon or Velcro?
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The interaction between endometrium and peritoneum |
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Working with the hypothesis that endometrium would have to attach to the peritoneal lining in order to form an endometriotic lesion we first showed that members of the integrin and cadherin family of proteins are expressed in endometriotic lesions and in cells and tissues that are potentially involved in the development of endometriosis (Van der Linden et al., 1994, 1995
). Since the mere presence of cell adhesion molecules (CAMs) in endometrium, menstrual tissue and endometriotic lesions does not prove the functional role of CAMs in the attachment of endometrium to peritoneum, we developed a functional in-vitro model to study the interaction between endometrium and peritoneum. Cyclic (i.e. biopsied) as well as menstrual (i.e. spontaneously shed) endometrium was used. In the early experiments the amniotic membrane was used as a model for peritoneum, stripped and unstripped, i.e. devoid of the epithelial lining and with an intact epithelial lining. Using immunohistochemistry we showed the amniotic membrane to be similar to the peritoneum, at the epithelial and subepithelial level (Van der Linden et al., 1996
). In later experiments fresh human peritoneum and cultured mesothelial cells, recovered from human omentum, were used.
Using the stripped and unstripped amnion model and early proliferative endometrium obtained with a Probet endometrial sampling device (Gynetic, Oisterwijk, The Netherlands), we showed that intact endometrial fragments, and not enzymatically digested epithelial and stromal cells, only adhered to the extracellular matrix side of the amnion and not to the epithelial side of the amnion, after culturing for 24 h. Adherence was assessed using immunohistochemistry and light microscopy (Van der Linden et al., 1996, 1998
). Both stromal and epithelial cells showed adherence. The functional role of integrins in this adhesion process was corroborated by results of experiments that blocked the integrins (Koks et al., 2000a
). The adhesion studies were extended in the same amniotic membrane model using scanning and transmission electron microscopy to determine the adhesion between endometrial fragments and the amnion (Groothuis et al., 1998
). Again the endometrial fragments were seen at the extracellular matrix side of the amnion.
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The role of an intact mesothelium |
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In a comparable experiment Witz and co-workers showed almost the same results and surprisingly came to the exact opposite conclusion (Witz et al., 1999). They used biopsied, cyclic (unfortunately not menstrual), mechanically dispersed, endometrium explanted on fresh human peritoneum and cultured it for 24 to 48 h. Using light and electron microscopy they showed that in 90% of instances the endometrium was on top of the extracellular matrix, while in 10% the mesothelium was present beneath the endometrium. These authors concluded that endometrium attaches to the mesothelium and rapidly invades through the mesothelium.
Results from experiments in cancer research underscore the importance of an intact mesothelial lining. The ability of human ovarian carcinoma cells derived from ascitic fluid to attach to a mesothelial cell monolayer grown on extracellular matrix or on extracellular matrix alone was quantitated by Niedbala and co-workers (1985) using 51Cr radio-labelled tumour cells. Tumour cell attachment was limited to areas of exposed extracellular matrix in lacerated mesothelium as assessed by phase contrast microscopy (Niedbala et al., 1985).
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Menstruum as the aggressor |
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We therefore tested the possible deleterious effect of the contents of menstrual effluent on mesothelial cells in co-culture with mesothelial cell monolayers. We showed that shed menstrual endometrium, menstrual endometrium in an insert, menstrual serum and conditioned medium of cultured menstrual tissue, lead to severe damage to the mesothelial cells. This suggests that the effect is at least partly paracrine in nature. The morphological changes were shown not to be primarily related to apoptosis or necrosis (Demir-Weusten et al., 2000).
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Conclusions |
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Acknowledgements |
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Notes |
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References |
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