Differential Expression And Regulation Of Prostaglandin E Synthase Genes In Rat Uterus During The Peri-Impantation Period

Prostaglandin E2 (PGE2) is considered important for reproduction in mammal. Cyclooxygenase (COX) can catalyze the bis-oxygenation of arachidonic acid leading to production of PGH2. PGE synthase (PGES) catalyzes the isomerization of PGH2 to PGE2. There are three isoforms of PGES, glutathione-dependent membrane-associated PGES (mPGES-1), glutathione-independent membrane-associated PGES (mPGES-2), and glutathione-dependent cytosolic PGES (cPGES). mPGES-1, an inducible perinuclear enzyme, is preferentially coupled with the inducible COX-2 to promote delayed PGE2 generation. mPGES-2 is expressed constitutively in wide variety of cells and tissues, which is linked with COX-1 and COX-2. cPGES, a constitutive enzyme expressed, is predominantly linked with the COX-1 to promote immediate PGE2 generation. Although PGES expression and regulation have been studied in mouse and bovine uteri during early pregnancy, they have not been reported in rat uterus. The aim of this study was to investigate the differential expression of mPGES-1 in rat uterus during early pregnancy, pseudopregnancy, delayed implantation and activation, artificial decidualization and inhibitor treatment by in situ hybridization and immunohistochemistry. In addition, the expression of cPGES and mPGES-2 protein was also examined in rat uterus during early pregnancy. There was no expression of mPGES-1 mRNA and protein in uteri from days 1 to 5 during early pregnancy. Both mPGES-1 mRNA and protein were strongly observed in the subluminal stroma exclusively surrounding the implanting blastocyst at implantation site, but not seen in the inter-implantation site on day 6 of pregnancy. Expression of mPGES-1 was detected in primary decidual zone from days 7 to 9 of pregnancy. mPGES-1 mRNA and protein were not seen in the pseudopregnant uteri. Under delayed implantation, mPGES-1 mRNA and protein were not detected in the uterus. Once delayed implantation was terminated by estrogen treatment 36 h later and embryo implantation initiated, mPGES-1 mRNA and protein were similar to the expression pattern on day 6 of pregnancy. mPGES-1 was also highly expressed in the artificially decidualized cells, but not in the control horn. Both RU486 and ICI 182,780 treatments on pregnant rats obviously blocked mPGES-1 protein expression of at implantation site. Expression of cPGES protein was not seen in the uterus from days 1 to 5 of pregnancy. On day 6 of pregnancy, cPGES protein was highly expressed in the luminal epithelium and stroma immediately surrounding the blastocyst. mPGES-2 protein was highly detected in the luminal epithelium and glandular epithelium from days 1 to 5 of pregnancy, and the expression of mPGES-2 protein was at a low level in the subluminal stroma at implantation site on day 6. From days 7 to 9 of pregnancy, the signals of cPGES and mPGES-2 protein were seen in the decidualized cells. In summary, the specific expression of mPGES-1, mPGES-2 and cPGES at the implantation site and in decidual cells in rat uterus suggests that PGES may play an important role during implantation and decidualization.