An increase in endometrial vascular permeability (EVP) occurs approximately 4 hours after the administration of a deciduogenic stimulus in rats sensitized for the decidual cell reaction. EVP precedes decidualization, in which the endometrial stromal cells proliferate and differentiate into decidual cells. Decidualization begins approximately 20 hours after a deciduogenic stimulus administration in rats. Recently, the cyclo-oxygenase (Ptgs) pathway and products have been investigated to elucidate their roles in decidualization. It has been proposed that the Ptgsproduct, prostacyclin, binds to the nuclear receptor, PPARD, which then heterodimerizes with RXRA to induce decidualization. However, the significance of these nuclear receptors in the early events of decidualization has not been sufficiently addressed. Our objectives are to characterize the expression patterns of Ppardand Rxrain the rat endometrium and to infuse synthetic ligands of these nuclear receptors into the rat uterus to assess the receptors functions during the early stages of decidualization. It is hypothesized that Ppardand Rxrasignificantly contribute to the early events of decidualization. Female Sprague-Dawley rats were ovariectomized and subjected to a hormone treatment to simulate pseudopregnancy. On the equivalent of Day 5 of pseudopregnancy, an intrauterine injection of sesame oil was administered to induce decidualization. Endometrial tissue was then collected at 2, 4, 8, 16, or 32 hours after the stimulation, with non-stimulated control tissues collected at 0, 8, and 32 hours. Semi-quantitative RT-PCR revealed no significant changes in mRNA levels for either receptor between times or between stimulated and non-stimulated samples. Western blot analysis revealed that PPARD protein levels did not change but RXRA levels were significantly increased at 16 hours. Immunohistochemical analysis showed that PPARD and RXRA were mainly expressed in the luminal and glandular epithelium, but not in the antimesometrial stroma, the region of the endometrium which initially undergoes decidualization. In addition, artificially stimulated endometrial samples from Day 5 to Day 10 of pseudopregnancy were subjected to western blot analysis and showed that PPARD levels did not significantly change while RXRA levels were significantly increased on Day 8 when compared to Days 5, 6, and 10. To test if synthetic ligands of the nuclear receptors had an effect on EVP, prostaglandin E2 (PTGER agonist), L165041 (PPARD selective agonist), docosahexanoic acid (DHA; RXRA agonist), and a 50% v/v DMSO/PBS vehicle control were infused, via osmotic pumps, into the uterine lumen of rats treated with indomethacin to inhibit endogenous prostaglandin production. Ten hours after the initiation of the infusion, rats were given an injection of Evans blue dye via the tail vein. Rats were then killed and whole uteri were collected and stored in formamide for dye extraction. This experiment showed that L165041 or DHA, infused separately or together, did not increase EVP, as indicated by uterine Evans blue dye concentrations, when compared to the vehicle control, whereas prostaglandin E2 infusion showed an increase in EVP. These results suggest that Ppardand Rxrado not have a role in the early processes of decidualization but may be involved in later processes. This project is supported by CIHR.