Introduction:Prostaglandins (PGs) are important regulators of the reproductive function. Using global transcriptome sequencing we have generated a library of genes regulated during the ovulatory process. Prostaglandin transporter (PGT)was among the highly up-regulated genes. We therefore hypothesize that PGT might have an important regulatory role in ovarian PGE2 metabolism and ovulation.
Aim:The aim of this study is to characterize the expression and function of PGT in the human ovarian follicles during the preovulatory period.
Materials&Methods:In vivoPGT expression in mural (MGCs) and cumulus cells (CCs)aspirated during IVF/IVM procedures were determined.Hormonal and signaling pathways regulations of PGT were studied using cultured MGCs treated withvarious activators /inhibitors.The functional role of PGT in PG regulation was studied in cultured MGCs.
Results:PGT expression was higher in MGCs of larger follicles and CCs of mature oocyte, compared to CCs of germinal vesicle oocytes. Thein vivoresults suggest that PGT is a LH/hCG target gene. LH/hCG dependent induction of PGT was confirmedin vitroat the mRNA and protein levels. Signaling assays demonstrate that PKA, PKC and ERK pathways are downstream mediators leading to PGT up-regulation. The addition of BCG, a known PGT blocking agent, results in elevation of extracellular PGE2 concentration, suggesting a role of PGT in PGE2 influx.
Conclusions:Taken together, we found that PGT is a new LH/hCG target ovulatory gene. PGT is involved in PGE2 uptake and therefore might be involved in PGE2 signal termination and in the regulation of PGE2 levels during final follicular maturation and ovulation.
