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Copenhagen,
Denmark
19 - 22 June 2005
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Cyr61
in endometrium of baboons with
induced endometriosis
I Gashaw [1],
JM Hastings [2], E Winterhager [1], AT Fazleabas
[2]
[1] University Hospital
Institute for Anatomy
Essen, Germany
[2] University
of Illinois
Department of Obstetrics and Gynecology
Chicago, USA
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Objective
Cyr61 (cysteine rich 61, CCN1), a member of the
CCN family of growth regulators, is a proangiogenic
factor that mediates diverse roles in development,
cell proliferation, and tumorigenesis. Previously,
CYR61 has been shown to be increased in human eutopic
as well as ectopic endometrium in patients with
endometriosis. We investigated the expression pattern
of Cyr61 in normal and endometriotic endometrium,
as well as ectopic endometrial lesions in a primate
model of experimentally induced endometriosis.
Materials and methods
Control endometrium was collected throughout the
cycle from 23 normal baboons. Matched eutopic and
ectopic endometrium was harvested from six baboons
1, 3, 6, 9 and 15 months post-inoculation and from
two baboons with spontaneously induced disease,
at 8–11 days post-ovulation. Cyr61 expression
was determined by real-time RT–PCR, immunohistochemistry
and western blot analysis.
Results
Endometrial Cyr61 mRNA expression underwent moderate
cyclical variation with highest levels seen at day
2 post-menses. The Cyr61 transcript was extensively
upregulated in the eutopic endometrium from all
baboons with induced endometriosis, as early as
one month post-inoculation. 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 with that of VEGF-A.
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 protein and mRNA 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.
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