title: Lysophosphatidic acid increases the production of pivotal mediators of decidualization and vascularization in the rat uterus.
abstract: BACKGROUND
  The decidual reaction and the formation of new vessels in the uterus are two crucial processes during embryo implantation. Previously, we observed that lysophosphatidic acid (LPA) increases cyclooxygenase-2 derived - prostaglandin E2 production during implantation in the rat uterus and that it augments the expression of decidualization (IGFBP-1) and vascularization (IL-10) markers. Both cyclooxygenase and nitric oxide synthase (NOS) are known enzymes involved in these processes. Thus, we became interested in studying which factors contribute to LPA receptor-specific role during the decidual and the vascular reaction at implantation.
  
  
  METHODS
  We adopted a pharmacological approach in vitro incubating the uterus from rats on day 5 of gestation (day of implantation) with LPA, DGPP (a highly selective antagonist of LPA3, an LPA receptor) and cyclooxygenase and NOS selective and non-selective inhibitors. We determined NOS activity, prostaglandin E2 production and IGFBP-1 and IL-10 expression to evaluate decidualization and vascularization.
  
  
  RESULTS
  We observed that LPA augmented the activity of the inducible NOS isoform through LPA1/LPA3. Inducible NOS activity participated in the induction of cyclooxygenase-2/prostaglandin E2 increase stimulated by LPA. Also, cyclooxygenase-2 derived prostaglandins mediated LPA-stimulatory action on NOS activity. Both cyclooxygenase-2 and inducible NOS mediated LPA effect on IGFBP-1 and IL-10 expression.
  
  
  CONCLUSIONS
  These results suggest the participation of LPA/LPA3 in the production of crucial molecules involved in vascularization and decidualization, two main processes that prepare the uterine milieu for embryo invasion during implantation.
authors.affiliation: Laboratorio de Fisiología y Farmacología de la Reproducción, CEFYBO CONICET - UBA, Buenos Aires, Argentina.
authors.forename: J S
authors.initials: JS
authors.lastname: Beltrame
authors.forename: M S
authors.initials: MS
authors.lastname: Sordelli
authors.forename: M
authors.initials: M
authors.lastname: Cella
authors.forename: S
authors.initials: S
authors.lastname: Perez Martinez
authors.forename: A M
authors.initials: AM
authors.lastname: Franchi
authors.forename: M L
authors.initials: ML
authors.lastname: Ribeiro
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D003656:Decidua / Q000098:blood supply* / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D010064:Embryo Implantation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008246:Lysophospholipids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D010929:Placentation; D011247:Pregnancy; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014599:Uterus / Q000098:blood supply* / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D015415:Biomarkers; D052246:Cyclooxygenase 2 Inhibitors; D004791:Enzyme Inhibitors; D018970:Insulin-Like Growth Factor Binding Protein 1; D008246:Lysophospholipids; D020033:Protein Isoforms; D049368:Receptors, Lysophosphatidic Acid; D016753:Interleukin-10; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D015232:Dinoprostone; C032881:lysophosphatidic acid
keywords: Cyclooxygenase-2; Decidualization; Implantation; Inducible nitric oxide synthase; Lysophosphatidic acid; Vascularization