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Hum. Reprod. Advance Access published online on July 8, 2004
Human Reproduction, doi:10.1093/humrep/deh408
© 2004 by European Society of Human Reproduction and Embryology
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Received November 20, 2003
Revised April 19, 2004
Accepted June 16, 2004

Article

Inhibiting MMP activity prevents the development of endometriosis in the chicken chorioallantoic membrane model

Annemiek W. Nap 1, Gerard A.J. Dunselman 1, Anton F.P.M. de Goeij 2, Johannes L.H. Evers 1, Patrick G. Groothuis 1*

1 Research Institute Growth and Development (GROW), Department of Obstetrics and Gynaecology, University Maastricht and University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands
2 Research Institute Growth and Development (GROW), Department of Pathology, University Maastricht and University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands

* To whom correspondence should be addressed. E-mail: patrick.groothuis{at}path.unimaas.nl.


  Abstract

BACKGROUND: Matrix metalloproteinases (MMPs) are essential for extracellular matrix remodelling and may contribute to the development of endometriosis. Transplantation of endometrium onto the chicken chorioallantoic membrane (CAM) results in endometriosis-like lesion formation, a process that requires extensive tissue remodelling. We investigated the expression of a wide range of MMPs in menstrual endometrium, endometriosis-like lesions in CAMs, in peritoneal endometriosis and in endometriosis in the rectovaginal space, as well as the function of MMPs in early lesion formation in the CAM model. METHODS: Expression of MMPs was evaluated by immunohistochemistry and MMP function was studied in the CAM by inhibiting MMP activity during lesion formation. RESULTS: Nearly all MMPs were present in all tissues studied. No significant differences in the expression of a majority of MMPs were found in endometriosis-like lesions in CAMs when compared with human endometriosis. Inhibition of MMP-1, -2, -3, -7 and -13 activities significantly impaired endometriosis-like lesion formation in CAMs. CONCLUSIONS: The MMP expression profiles of experimentally induced endometriosis in CAMs and human endometriosis are similar. The prevention of endometriosis-like lesion formation in the CAM by inhibiting MMP activity strongly suggests that MMPs have a function in the early development of endometriotic lesions.

Keywords: chorioallantoic membrane model; endometriosis; endometrium; invasion; matrix metalloproteinase.
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