PLATFORM SESSION 20: FEMALE REPRODUCTIVE TRACT 2
Chair: Brenner, Robert1, 1
Co-chair: Bowen-Shauver, Jennifer1, 1
2:00 PM-4:00 PM
(440) HORMONAL REGULATION OF MATRIX METALLOPROTEINASE ENZYMES AND BLEEDING IN XENOGRAFTS OF MACAQUE ENDOMETRIOSIS.
Slayden, Ov1, Brenner, Robert1, 1 Division of Reproductive Sciences, Beaverton, OR
ABSTRACT- RAG-2 null mice, which lack T and B lymphocytes, can sustain xenografts for longer periods than other immunodeficient mouse strains. We studied hormonal control of macaque endometriotic xenografts over several menstrual cycles in this strain. Explants of ectopic endometriotic tissues from 3 rhesus macaques were transplanted subcutaneously into ovariectomized RAG- 2 null mice (6 mice/donor; 8 grafts/mouse). The acceptance rate of grafts was >80%. Implants (Innovative Research of America) releasing estradiol and progesterone (P) were used to create two artificial 28-day menstrual cycles in the mice. At the end of the second cycle the P implants were removed and grafts were obtained on day 0 (secretory phase), day 3 and 5 (premenstrual and menstrual), and day 14 (proliferative phase) of the third artificial cycle. 62% of the grafts were bleeding on days 3 and 5 after P withdrawal. Total RNA was harvested from some grafts, labeled by reverse transcription with 32P, and assayed on commercially prepared low-density nylon cDNA arrays (SuperArrays, Inc). Hybridization analysis revealed that the expression of 10 MMP enzymes (MMP-1, 2, 3, 7, 10, 11, 15, 16, 26; and MT1-MMP) and TIMP-1 was significantly greater (P<0.05) in the endometriotic xenografts on days 3 and 5 than on day 0. Expression of these MMP transcripts declined substantially by day 14. These data represent the first experimental evidence that endometriotic xenografts can be hormonally cycled in RAG-2 null mice, and that P-withdrawal can induce both up-regulation of MMP expression and bleeding in these grafts. Xenografts of endometriosis in RAG-2 null mice provide a unique model for study of factors affecting this disease. Supported by HD39363 (ODS) and RR00163.
KEY WORDS: endometriosis, MMPs, xenografts, macaque