PROSTAGLANDIN E-2 RECEPTOR SUBTYPE EP2 GENE-EXPRESSION IN THE MOUSE UTERUS COINCIDES WITH DIFFERENTIATION OF THE LUMINAL EPITHELIUM FOR IMPLANTATION

Among the PGs, PGE(2) is considered especially important for implantat ion and decidualization. Four major PGE(2) receptor subtypes, EP1, EP2 , EP3, and EP4, mediate various PGE(2) effects via their coupling to d istinct signaling pathways. Previously, we have shown that the EP1, EP 3, and EP4 genes are expressed in the periimplantation mouse uterus in a spatio-temporal manner, suggesting compartmentalized actions of PGE (2) during this period. In this study, we examined the expression of t he EP2 gene in the mouse uterus during the periimplantation period (da ys 1-8) and during experimentally induced progesterone (P-4)-maintaine d delayed implantation and its resumption by 17 beta-estradiol (E-2). We also examined its regulation in the uterus by ovarian steroid hormo nes. Our results establish that EP2 messenger RNA (mRNA) is expressed exclusively in the luminal epithelium primarily on day 4 (the day of i mplantation) and day 5 (early implantation) of pregnancy. In (P-4)-mai ntained delayed implanting mice, EP2 mRNA was present in the luminal e pithelium, and the expression was further enhanced regardless of the l ocation of the blastocysts after reinitiation of implantation. This ob servation suggests little or no embryonic influence in regulating EP2 expression and, instead, shows its regulation by P-4 and E-2. Indeed, treatment with E-2 and/or P-4 exhibited unique regulation of this gene . The treatment of adult ovariectomized mice with E-2 down-regulated t he basal levels of EP2 mRNA, whereas that with P-4 up-regulated its le vels in the luminal epithelium. The up-regulation of EP2 mRNA levels b y P-4 was further augmented by superimposition of the E-2 treatment, s ug gesting a synergistic interaction between E-2 and P-4 in regulating this gene in the uterus. Collectively, the results suggest that EP2 c ould be a potential mediator of PGE(2) actions in regulating luminal e pithelial differentiation and serve as a marker for uterine receptivit y for implantation.