Differential Expression And Regulation Of Prostaglandin Transporter And Metabolic Enzymes In Mouse Uterus During Early Pregnancy

Prostaglandins (PGs) are essential for embryo implantation and decidualization. However, PGspredominate as charged anions in physiological conditons and traverse poorly across the cellmembrane by simple diffusion despite their lipid nature. It has been shown that prostaglandintransporter (PGT) primarily mediate PGE2 and PGF2αtransport across the plasma membrane.Locally enzymanie inactivation of PGs is also necessary for their signal termination. Prostaglandinbiosynthesis and signaling in mammalian uterus during early pregnancy have been studiedthoroughly, but the mechanism of prostaglandin transport and metabolism in mouse uterus is stillunknown. The aim of this study was to investigate PGT, 15-PGDH and CBR1 expression in themouse uterus during early pregnancy and their regulation in related models of pseudopregnancy,delayed implantation, artificial decidualization, steroid hormone treatment by in situ hybridization,RT-PCR and immunohistochemistry. PGT mRNA was not detected, but PGT protein was expressedat a basal level from days 1 to 4 of pregnancy. When embryo implanted on day 5, PGT mRNA andprotein were strongly detected in the sub-luminal stroma immediately surrounding the implantedblastocyst. The data from the pseudopregnancy and delayed implantation suggested that theexpression of PGT was induced by active blastocyst. There was a high level of PGT expression inthe primary decidual zone on days 6 to 8 of pregnancy and in artificially induced decidua.Intrauterine injected BrCG, a nonspecifie inhibitor of PGT transport, almost inhibit embryoimplantation completely. 15-PGDH and CBR1 mRNA signals appeared in glandular epithelium ofuterus on day 4 of pregnancy. On day 5, 15-PGDH mRNA was located in luminal epithelium ofimplantation chamber. On days 6 to 8, expression of 15-PGDH was concentrated at mater-fetalinterface and CBR1 mRNA was detected mainly in postimplantation embryo. Based on our results,dynamically expression of PGT and PG metabolic enzymes in uterus during early pregnancysuggested their roles in regulation of local PG signaling for embryo implantation anddecidualization.