Differential expression and regulation of cylooxygenases, prostaglandin E synthases and prostacyclin synthase in rat uterus during the peri-implantation period

Abstract

It has been shown that both prostaglandin I2 (PGI2) and PGE2 are essential for mouse implantation, whereas only PGE2 is required for hamster implantation. To date, the expression and regulation of cyclooxygenase (COX) and prostaglandin E synthase (PGES), which are responsible for PGE2 production, have not been reported in the rat. The aim of this study was to examine the expression pattern and regulation of COX-1, COX-2, membrane-associated PGES-1 (mPGES-1), mPGES-2 and cytosolic PGES (cPGES) in rat uterus during early pregnancy and pseudopregnancy, and under delayed implantation. At implantation site on day 6 of pregnancy, COX-1 immunostaining was highly visible in the luminal epithelium, and COX-2 immunostaining was clearly observed in the subluminal stroma. Both mPGES-1 mRNA and protein were only observed in the subluminal stroma surrounding the implanting blastocyst at the implantation site on day 6 of pregancy , but were not seen in the inter-implantation site on day 6 of pregnancy and on day 6 of pseudopregnancy. Our data suggest that the presence of an active blastocyst is required for mPGES-1 expression at the implantation site. When pregnant rats on day 5 were treated with nimesulide for 24 h, mPGES-1 protein expression was completely inhibited. cPGES immunostaining was clearly observed in the luminal epithelium and subluminal stromal cells immediately surrounding the implanting blastocyst on day 6 of pregnancy. mPGES-2 immunostaining was clearly seen in the luminal epithelium at the implantation site. Additionally, immunostaining for prostaglandin I synthase (PGIS) was also strongly detected at the implantation site. In conclusion, our results indicate that PGE2 and PGI2 should have a very important role in rat implantation.

Expression patterns and role of prostaglandin-endoperoxide synthases, prostaglandin E synthases, prostacyclin synthase, prostacyclin receptor, peroxisome proliferator-activated receptor delta and retinoid x receptor alpha in rat endometrium during artificially-induced decidualization

“…No signal of PTGS2 was detected in the luminal epithelium at any time. These results agree with those reported by Cong et al (2006) where in pregnant rats, PTGS2 protein was localized in the stromal cells on the morning of day 5, before the initiation of implantation, and continued to be expressed in the stroma at both implantation sites and interimplantation sites through to day 6, after initiation of implantation had occurred.…”

“…The results in rats also differ from those in mice, where PTGS2 was localized to the luminal epithelium, underlying stroma and in glandular epithelium 24 h after a deciduogenic stimulus was given (at the time when decidualization would have started) and then dramatically decrease at 48 and 120 h (Pakrasi & Jain 2008). In our study, as well as in those of Wang et al (2004) and Cong et al (2006), there was a gradual increase in the number of PTGS2 positive stromal cells as shown by immunostaining. These results agree also with what is reported in pregnant mice, where PTGS2 protein gradually localizes in stromal cells and the primary decidual zone surrounding the implanting embryos after implantation has been initiated (Lim et al 1997).…”

“…The levels of PTGS1 protein did not change at any time after the deciduogenic stimulus, indicating that is not regulated during the increase in EVP or the initiation of decidualization in rat endometrium. A recent report conducted in pregnant rats indicated that PTGS1 protein is localized in the luminal epithelium at the implantation sites on day 4 and day 5, prior to implantation (Cong et al 2006). On day 6 of pregnancy, after the increase in EVP and initiation of decidualization have already occurred, PTGS1 protein was localized to the luminal epithelium and at a basal level in the subluminal stroma (Cong et al 2006).…”

“…A recent report conducted in pregnant rats indicated that PTGS1 protein is localized in the luminal epithelium at the implantation sites on day 4 and day 5, prior to implantation (Cong et al 2006). On day 6 of pregnancy, after the increase in EVP and initiation of decidualization have already occurred, PTGS1 protein was localized to the luminal epithelium and at a basal level in the subluminal stroma (Cong et al 2006). In our study, PTGS1 protein was localized to the luminal epithelial cells, glandular epithelial and the stromal cells before, during and after the increase in EVP and the initiation of decidualization, suggesting that it could have a role in both of these events in the rat endometrium.…”

“…In previous in vitro studies of early stages of the inflammatory process and PGE 2 production, PTGES3 was found to be coupled to PTGS1 , whereas in delayed inflammatory responses, PTGES was the only enzyme associated with PTGS2 . Moreover, a recent study in rat endometrium during the peri-implantation period suggested that because there is a co-localization of PTGS2 and PTGES in the subluminal stromal cells and also a co-localization of PTGS1, PTGES3, and PTGES2 in the luminal epithelium surrounding the implantating blastocyst, PGE 2 could be produced through PTGS2/PTGES, PTGS1/PTGES3, and/or PTGS1/PTGES2 pathways (Cong et al 2006). However, it is still unclear which specific PTGS is interacting with which PTGES in the rat endometrium to increase PGE 2 production during the initiation of the decidualization.…”