title: Epidermal growth factor: Porcine uterine luminal epithelial cell migratory signal during the peri-implantation period of pregnancy.
abstract: The majority of early conceptus mortality in pregnancy occurs during the peri-implantation period, suggesting that this period is important for conceptus viability and the establishment of pregnancy. Successful establishment of pregnancy in all mammalian species depends on the orchestrated molecular events that transpire at the conceptus-uterine interface during the peri-implantation period of pregnancy. This maternal-conceptus interaction is especially crucial in pigs because they have a non-invasive epitheliochorial placentation during a protracted peri-implantation period. During the pre-implantation period of pregnancy, conceptus survival and the establishment of pregnancy depend on the developing conceptus receiving an adequate supply of histotroph which contains a wide range of nutrients and growth factors. Evidence links epidermal growth factor (EGF) to embryogenesis or implantation in various mammalian species. EGF exhibits potential growth-promoting activities on the conceptus and endometrium; however, in the case of pigs, little is known its functions, especially their regulatory mechanisms at the maternal-conceptus interface. EGF receptor (EGFR) mRNA and protein are abundant in endometrial luminal (LE) and glandular (GE) epithelia and conceptus trophectoderm on Days 13-14 of pregnancy, suggesting that EGF provides an autocrine signal to uterine LE and GE just prior to implantation. Therefore, the objectives of this study were to determine: 1) the potential intracellular signaling pathways responsible for the activities of EGF in porcine uterine LE (pLE) cells; and 2) the changes in cellular activities induced by EGF. EGF treatment of pLE cells increased the abundance of phosphorylated (p)-ERK1/2, p-P70RSK and p-RPS6 compared to that for control cells. Furthermore, EGF-stimulated phosphorylation of ERK1/2 MAPK was inhibited in pLE cells transfected with an EGFR siRNA compared with control siRNA-transfected pLE cells. Moreover, EGF stimulated migration of pLE cells, but this stimulatory effect was blocked by U0126, a pharmacological inhibitor or ERK1/2 MAPK. Collectively, these results provide new insights into mechanisms whereby EGF regulates development of the peri-implantation uterine LE at the fetal-maternal interface. These results indicate that endometrial- and/or conceptus derived EGF effects migration of uterine LE and that those stimulatory effects are regulated via the ERK1/2 MAPK pathway during early pregnancy in pigs.
authors.affiliation: Department of Animal Resources Science, Dankook University, Cheonan, Republic of Korea.
authors.forename: Wooyoung
authors.initials: W
authors.lastname: Jeong
authors.affiliation: Department of Animal Resources Science, Dankook University, Cheonan, Republic of Korea.
authors.forename: Seoungo
authors.initials: S
authors.lastname: Jung
authors.affiliation: Center for Animal Biotechnology and Genomics and Department of Animal Science, Texas A&M University, College Station, TX, USA.
authors.forename: Fuller W
authors.initials: FW
authors.lastname: Bazer
authors.affiliation: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea. Electronic address: ghsong@korea.ac.kr.
authors.forename: Gwonhwa
authors.initials: G
authors.lastname: Song
authors.affiliation: Department of Animal Resources Science, Dankook University, Cheonan, Republic of Korea. Electronic address: jinyoungkim@dankook.ac.kr.
authors.forename: Jinyoung
authors.initials: J
authors.lastname: Kim
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects*; D010064:Embryo Implantation / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D038601:Ribosomal Protein S6 / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D034421:Sus scrofa; D014599:Uterus / Q000166:cytology*
chemical_list: D002070:Butadienes; D009570:Nitriles; D038601:Ribosomal Protein S6; C113580:U 0126; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D038762:Ribosomal Protein S6 Kinases, 70-kDa
keywords: EGF; Migration; Pig; Trophoblast; Uterine luminal epithelium