PRECLINICAL STUDIES ON NONHUMAN PRIMATE ENDOMETRIAL XENOGRAFTS

Oregon Health & Science University, Portland OR

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Endometriosis is a condition where endometrium-like tissue forms lesions at sites outside the uterus. Our goal is to test potential therapies for endometriosis. To do this we have developed a model in which macaque endometrium is transplanted into immunodeficient SCID mice, which are incapable of rejecting xenografts. The endometrial xenografts grow in response to estradiol (E2) and undergo cyclic breakdown similar to endometriosis in women. We tested the effects of three antiestrogenic (anti estrogen receptor alpha) selective estrogen receptor modulators (SERMs) and report that these SERMS suppress growth of ectopic macaque endometrium. We also tested 3 proprietary ER beta agonists provided by Bayer Schering Pharma AG and report that ER beta agonists do not inhibit the establishment of ectopic endometrium in these mice. We then tested inhibitors of vascular endothelial growth factor (VEGF)-A and endocrine gland (EG)-VEGF, and report that both inhibitors blocked graft acceptance and growth.