title: Autocrine and paracrine mechanisms of prostaglandin E₂ action on trophoblast/conceptus cells through the prostaglandin E₂ receptor (PTGER2) during implantation.
abstract: The conceptus and endometrium secrete large amounts of prostaglandin E₂ (PGE₂) into the porcine uterine lumen during the periimplantation period. We hypothesized that PGE₂ acts on conceptus/trophoblast cells through auto- and paracrine mechanisms. Real-time RT-PCR analysis revealed that PGE₂ receptor (PTGER)2 mRNA was 14-fold greater in conceptuses/trophoblasts on days 14-25 (implantation and early placentation period) vs preimplantation day 10-13 conceptuses (P < .05). Similarly, expression of PTGER2 protein increased during implantation. Conceptus expression of PTGER4 mRNA and protein did not differ on days 10-19. PGE₂ stimulated PTGER2 mRNA expression in day 15 trophoblast cells through PTGER2 receptor signaling. PGE₂ elevated aromatase expression and estradiol-17β secretion by trophoblast cells. Moreover, PGE₂ and the PTGER2 agonist, butaprost, increased the adhesive capacity of both human HTR-8/SVneo trophoblast and primary porcine trophoblast cells to extracellular matrix. This PGE₂-induced alteration in trophoblast cell adhesion to extracellular matrix was abolished by incubation of these cells with AH6809 (PTGER2 antagonist), ITGAVB3-directed tetrapeptide arg-gly-asp-ser or integrin ITGAVB3 antibody. PGE₂ stimulated adhesion of porcine trophoblast cells via the estrogen receptor and MEK/MAPK signaling pathway. PGE₂ induced phosphorylation of MAPK1/MAPK3 through PTGER2 and up-regulated expression of cell adhesion proteins such as focal adhesion kinase and intercellular adhesion molecule-1. Our study indicates that elevated PGE₂ in the periimplantation uterine lumen stimulates conceptus PTGER2 expression, which in turn promotes trophoblast adhesion via integrins, and synthesis and secretion of the porcine embryonic signal estradiol-17β. Moreover, the mechanism through which PGE₂ increases trophoblast adhesion is not species specific because it is PTGER2- and integrin-dependent in both porcine and human trophoblast cells.
authors.affiliation: Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Tuwima 10, 10-748 Olsztyn, Poland. waclawik@pan.olsztyn.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Waclawik
authors.forename: Piotr
authors.initials: P
authors.lastname: Kaczynski
authors.forename: Henry N
authors.initials: HN
authors.lastname: Jabbour
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D003433:Crosses, Genetic; D015232:Dinoprostone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000187:drug effects / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019899:Paracrine Communication / Q000187:drug effects; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034421:Sus scrofa; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D016023:Integrins; C545644:PTGER2 protein, human; D011448:Prostaglandin Antagonists; D058307:Receptors, Prostaglandin E, EP2 Subtype; D004958:Estradiol; D015232:Dinoprostone