title: Prokineticin 1 mediates fetal-maternal dialogue regulating endometrial leukemia inhibitory factor.
abstract: Implantation requires communication between a receptive endometrium and a healthy blastocyst. This maternal-embryonic crosstalk involves local mediators within the uterine microenvironment. We demonstrate that a secreted protein, prokineticin 1 (PROK1), is expressed in the receptive endometrium and during early pregnancy. PROK1 induces expression of leukemia inhibitory factor (LIF) in endometrial epithelial cells and first trimester decidua via a Gq-Ca(2+)-cSrc-mitogen-activated protein kinase kinase-mediated pathway. We show that human embryonic chorionic gonadotropin (hCG) induces sequential mRNA expression of PROK1 and LIF in an in vivo baboon model, in human endometrial epithelial cells, and in first-trimester decidua. We have used micro RNA constructs targeted to PROK1 to demonstrate that hCG-mediated LIF expression in the endometrium is dependent on prior induction of PROK1. Dual immunohistochemical analysis colocalized expression of the luteinizing hormone/chorionic gonadotropin receptor, PROK1, PROKR1, and LIF to the glandular epithelial cells of the first trimester decidual tissue. PROK1 enhances adhesion of trophoblast cells to fibronectin and laminin matrices, which are mediated predominantly via LIF induction. These data describe a novel signaling pathway mediating maternal-embryonic crosstalk, in which embryonic hCG via endometrial PROK1 may play a pivotal role in enhancing receptivity and maintaining early pregnancy.
authors.affiliation: MRC Human Reproductive Sciences Unit, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
authors.forename: Jemma
authors.initials: J
authors.lastname: Evans
authors.forename: Rob D
authors.initials: RD
authors.lastname: Catalano
authors.forename: Pamela
authors.initials: P
authors.lastname: Brown
authors.forename: Rob
authors.initials: R
authors.lastname: Sherwin
authors.forename: Hilary O D
authors.initials: HO
authors.lastname: Critchley
authors.forename: Asgerally T
authors.initials: AT
authors.lastname: Fazleabas
authors.forename: Henry N
authors.initials: HN
authors.lastname: Jabbour
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology* / Q000502:physiology; D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000032:analysis; D010064:Embryo Implantation; D004717:Endometrium / Q000166:cytology* / Q000502:physiology; D004847:Epithelial Cells; D005260:Female; D005768:Gastrointestinal Hormones; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D053605:Leukemia Inhibitory Factor / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D010215:Papio; D019899:Paracrine Communication / Q000502:physiology*; D011247:Pregnancy; D043562:Receptors, G-Protein-Coupled; D011974:Receptors, LH / Q000032:analysis; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / Q000032:analysis / Q000502:physiology*
chemical_list: D006063:Chorionic Gonadotropin; D005768:Gastrointestinal Hormones; D053605:Leukemia Inhibitory Factor; C467610:PROK1 protein, human; C470837:PROKR1 protein, human; D043562:Receptors, G-Protein-Coupled; D011974:Receptors, LH; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived