27 - 30 May 2005

ENDOMETRIOSIS INCREASES THE LEVEL OF ANGIOGENIC ACTIVE CYR61 IN ENDOMETRIUM OF BABOONS Isabella Gashaw [1], Julie M. Hastings [2], Elke Winterhager [1], Asgerally T. Fazleabas [2] [1] Institute for Anatomy University Hospital Essen Germany [2] Department of Obstetrics and Gynecology University of Illinois Chicago, IL USA

The expression of Cyr61 (cysteine-rich, angiogenic inducer, 61, CCN1) has been investigated in endometria of 23 healthy olive baboons (papio anubis), in 6 baboons with induced endometriosis at different time points of disease as well as in 2 animals with spontaneously developed disease. Endometriotic eutopic and ectopic endometrium was harvested at 8-11 days post-ovulation and compared to cycle matched normal endometrium. Cyr61 expression was determined by real time RT-PCR, immunohistochemistry and western blot analysis.

Endometrial Cyr61 mRNA expression underwent moderate cyclical variation with a significant 7.3-fold increase detected at day 2 post menses (P < 0.001) when compared to endometrium from proliferative and secretory phase. The Cyr61 transcript was extensively up-regulated in the eutopic endometrium from all baboons with induced endometriosis, as early as one month post inoculation of tissue into peritoneal cavity. Cyr61 expression then decreased throughout progression of disease, but remained higher than that seen in control tissues. Similarly to humans, ectopic endometriotic lesions showed a further increase of Cyr61 mRNA, with highest levels found in red lesions (up to 74-fold compared to matched eutopic endometrium). Moreover, the expression of Cyr61 correlated significantly to that of VegfA.

Immunohistochemistry revealed the presence of Cyr61 protein in glandular and luminal epithelial cells of the eutopic endometrium, together with secretion into the lumen. In the endometriotic lesions, Cyr61 expression was evident in both the epithelial cells of the glands and the blood vessels.

Conclusion: Increased levels of Cyr61 correlate with the development of endometriosis in baboons, similarly to humans. The increase of Cyr61 in eutopic endometrium of baboons following peritoneal inoculation with menstrual endometrium provides evidence for a feedback mechanism from the resulting lesions to a shift in gene expression patterns in the eutopic endometrium.

List of abstracts from the 3rd International Conference on the Female Reproductive Tract