title: Prostaglandin F2α promotes angiogenesis and embryo-maternal interactions during implantation.
abstract: Implantation in humans and other mammals is a critical period during which high embryonic mortality rates occur. Prostaglandins (PGs) are key mediators regulating interactions between the reproductive tract and the conceptus (embryo with extraembryonic membranes). Although the significance of PGF2α as a regulator of corpus luteum regression is well established, the role of its high amounts in the uterine lumen in most mammals, regardless of placentation type, during the implantation period remains unresolved. We hypothesized that PGF2α acting as an embryonic signal mediator contributes to pregnancy establishment. Using a porcine model, we demonstrated that the conceptus and its signal (estradiol-17β) elevated endometrial expression of PGF2α receptor (PTGFR) in vivo and in vitro PTGFR protein was expressed mainly in luminal epithelial (LE) and glandular epithelial cells and blood vessels in the endometrium. PGF2α stimulated the MAPK1/3 pathway in endometrial LE cells that coincided with elevated gene expression and secretion of endometrial vascular endothelial growth factor A (VEGFA) protein. PGF2α-PTGFR and adenylyl cyclase signaling were involved in this process. PGF2α-induced VEGFA acting through its receptors stimulated proliferation of endometrial endothelial cells. Moreover, PGF2α elevated gene expression of biglycan, matrix metalloproteinase 9, transforming growth factor β3, and interleukin 1α in the endometrium. In summary, our study indicates that PGF2α participates in pregnancy establishment by promoting angiogenesis and expression of genes involved in tissue remodeling and conceptus-maternal interactions in porcine endometrium during early pregnancy.
authors.affiliation: Institute of Animal Reproduction and Food Research of Polish Academy of SciencesTuwima 10, 10-748 Olsztyn, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kaczynski
authors.affiliation: Vetsuisse FacultyInstitute of Veterinary Anatomy, University of Zurich, Zurich, Switzerland.
authors.forename: M P
authors.initials: MP
authors.lastname: Kowalewski
authors.affiliation: Institute of Animal Reproduction and Food Research of Polish Academy of SciencesTuwima 10, 10-748 Olsztyn, Poland waclawik@pan.olsztyn.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Waclawik
mesh_terms: D000020:Abortifacient Agents, Nonsteroidal / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D015237:Dinoprost / Q000494:pharmacology*; D010064:Embryo Implantation / Q000187:drug effects*; D004622:Embryo, Mammalian / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects; D004717:Endometrium / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007124:Immunoenzyme Techniques; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine
chemical_list: D000020:Abortifacient Agents, Nonsteroidal; D012333:RNA, Messenger; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; D015237:Dinoprost