O-059 Altered Endometrial Expression of Endothelial Nitric Oxide Synthase

Objectives: Nitric oxide (NO) is a vasodilator synthesized from Larginine through the action of nitric oxide synthase (NOS). Recently we demonstrated that the endometrial expression of eNOS protein was higher during the secretory phase as compared to the proliferative phase, and exogenous steroids influenced eNOS expression. Based on these observations we postulated that NO may play a significant role in endometrial physiology through regulation of local blood flow. The purpose of this study was to determine if changes in the expression of endometrial eNOS in women with endometriosis could be a contributing factor to the pathogenesis of this disease. Design: Endometrial biopsies were obtained from women undergoing laparascopy for infertility 8 ‐10 days post LH surge. Subjects were assigned to a control (n59) or endometriosis group (n531) based on the surgical findings. In a separate study peritoneal fluid was obtained for NO measurement from women undergoing laparascopy for infertility. IRB approval was obtained for both studies. Materials and Methods: Tissue sections from the same luteal phase endometrial biopsies were immunostained for both eNOS and b3 integrin using human directed monoclonal antibodies. Intensity and distribution of staining was determined using the semiquantitative HSCORE. Peritoneal fluid levels of NO were measured by a NO analyzer. Results: A four fold (P,0.0001) and 1.5 fold higher (P,0.0002) eNOS staining intensity was found in the luminal and glandular epithelium respectively of women with endometriosis as compared to the control group. No differences in stromal eNOS staining was detected between the two groups. Peritoneal fluid levels of NO did not differ in women with and without endometriosis. A significant positive correlation (r5.37, P,0.05) between glandular eNOS protein and b3 was found in women with endometriosis but not in the control group. There were no other significant correlations found between eNOS and b3 expression in other uterine compartments in either group. Conclusions: A highly significant site-specific increase in endometrial eNOS expression was detected in women with endometriosis. Peritoneal fluid levels of NO, however, were not altered in women with endometriosis. A positive correlation between glandular eNOS and b3 was found only in women with endometriosis. These results suggest increased endometrial expression of eNOS in women with endometriosis may contribute to the pathogenesis of this disease, and point to an interaction between eNOS and b3 in glandular epithelium.