[O-309] ENDOMETRIAL CXCL13 IS ABERRANTLY EXPRESSED IN HUMANS AND MACAQUES WITH ENDOMETRIOSIS.
J. M. Franasiak, O. Slayden, B. A. Lessey, L. Yuan, M. A. Fritz, S. L. Young. Ob/Gyn, UNC School of Medicine, Chapel Hill, NC; Ob/Gyn, Greenville Hospital System, Greenville, SC; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR.
OBJECTIVE: CXCL13, a regulator of mucosal immunity and putative regulator of embryo implantation, is highly secreted by human endometrial epithelium. We have previously reported cyclic changes in endometrial expression of CXCL13 in normal human subjects, with maximal expression in the mid-secretory phase. Herein, we compare CXCL13 expression between control and endometriosis human (H) and rhesus macaque (M) subjects.
MATERIALS AND METHODS: Eutopic endometrial CXCL13 expression was determined by real-time RT-PCR analysis and localized with immunohistochemistry in H, infertile, stage 1-4 endometriosis subjects (n=15) and normal controls (n=40) as well as in M stage 4 endometriosis subjects (n=14) and normal controls (n=12). Cycle phase in H was determined by urine LH detection. M with naturally-acquired, severe endometriosis were subjected to pituitary down-regulation by Antide, followed by 14 days of physiological estrogen exposure followed by 14 days of either physiological estrogen (proliferative) or estrogen+progesterone (late secretory). Pairwise comparisons: Mann-Whitney U test. Significance: p<0.05.
RESULTS: In proliferative-phase, eutopic endometrium, both H and M subjects demonstrated significantly increased CXCL13 mRNA expression (10.5- and 1.8-fold, respectively) as compared to controls. In the M there was also a significant 3.8-fold increase in CXCL13 expression in late-secretory phase endometriosis subjects versus controls. No difference was seen in H mid-secretory phase samples. CXCL13 protein immunolocalized to glandular and luminal epithelium with intensities proportional to changes in mRNA levels.
CONCLUSION: The eutopic endometrium of both humans and macaques with naturally-occuring endometriosis demonstrate increased CXCL13 expression. The cross-species and cross-stage concordance supports the hypothesis that eutopic CXCL13 expression is a robust disease marker and suggests that CXCL13 plays a pathophysiologic role in endometriosis.
Supported by: UNC REI & NIH/NICHD R01HD067721.
Wednesday, October 24, 2012 4:15 PM
Oral Session: Endometriosis