title: Endogenous lysophosphatidic acid participates in vascularisation and decidualisation at the maternal-fetal interface in the rat.
abstract: Lysophosphatidic acid (LPA) affects several female reproductive functions through G-protein-coupled receptors. LPA contributes to embryo implantation via the lysophospholipid LPA3receptor. In the present study we investigated the participation of endogenous LPA signalling through the LPA3receptor in vascularisation and decidualisation, two crucial events at the maternal-fetal interface. Pregnant rats were treated with diacylglycerol pyrophosphate (DGPP), a highly selective antagonist of LPA3receptors, on Day 5 of gestation. Pregnant rats received intrauterine (i.u.) injections of single doses of DGPP (0.1mgkg-1) in a total volume of 2μL in the left horn (treated horn) in the morning of GD5. DGPP treatment produced aberrant embryo spacing and increased embryo resorption. The LPA3receptor antagonist decreased the cross-sectional length of the uterine and arcuate arteries and induced histological anomalies in the decidua and placentas. Marked haemorrhagic processes, infiltration of immune cells and tissue disorganisation were observed in decidual and placental tissues from sites of resorption. The mRNA expression of three vascularisation markers, namely interleukin 10 (Il10), vascular endothelial growth factor (Vegfa) and vascular endothelial growth factor receptor 1 (Vegfr1), was reduced at sites of resorption from Day 8. The results show that the disruption of endogenous LPA signalling by blocking the LPA3receptor modified the development of uterine vessels with consequences in the formation of the decidua and placenta and in the growth of embryos.
authors.affiliation: Laboratorio de Fisiología y Farmacología de la Reproducción, Centre for Pharmacological and Botanicals Studies (CONICET - Facultad de Medicina, University of Buenos Aires), Paraguay 2155, 16th floor, Buenos Aires, Argentina.
authors.forename: Micaela S
authors.initials: MS
authors.lastname: Sordelli
authors.affiliation: Laboratorio de Fisiología y Farmacología de la Reproducción, Centre for Pharmacological and Botanicals Studies (CONICET - Facultad de Medicina, University of Buenos Aires), Paraguay 2155, 16th floor, Buenos Aires, Argentina.
authors.forename: Jimena S
authors.initials: JS
authors.lastname: Beltrame
authors.affiliation: Laboratorio de Fisiopatología Molecular, Cátedra de Fisiopatología, Departamento de Ciencias Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Elsa
authors.initials: E
authors.lastname: Zotta
authors.affiliation: Laboratorio de Farmacología de Receptores, Departamento de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Natalia
authors.initials: N
authors.lastname: Gomez
authors.affiliation: Laboratorio de Inmunofarmacología Tumoral, CEFYBO (CONICET - Facultad de Medicina, UBA).
authors.forename: Ganna
authors.initials: G
authors.lastname: Dmytrenko
authors.affiliation: Laboratorio de Inmunofarmacología Tumoral, CEFYBO (CONICET - Facultad de Medicina, UBA).
authors.forename: María Elena
authors.initials: ME
authors.lastname: Sales
authors.affiliation: Charité Centrum 12 für Innere Medizin und Dermatologie, Reproductive Medicine Research Group, University Medicine of Berlin, Berlin, Germany.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Blois
authors.affiliation: Laboratorio de Farmacología de Receptores, Departamento de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Carlos
authors.initials: C
authors.lastname: Davio
authors.affiliation: Laboratorio de Biología de la Reproducción en Mamíferos, CEFYBO (CONICET - Facultad de Medicina, UBA), Buenos Aires, Argentina.
authors.forename: Silvina Perez
authors.initials: SP
authors.lastname: Martinez
authors.affiliation: Laboratorio de Fisiopatología de la Preñez y al Parto, CEFYBO (CONICET - Facultad de Medicina, UBA), Buenos Aires, Argentina.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Franchi
authors.affiliation: Laboratorio de Fisiología y Farmacología de la Reproducción, Centre for Pharmacological and Botanicals Studies (CONICET - Facultad de Medicina, University of Buenos Aires), Paraguay 2155, 16th floor, Buenos Aires, Argentina.
authors.forename: María L
authors.initials: ML
authors.lastname: Ribeiro
mesh_terms: D000818:Animals; D003656:Decidua / Q000187:drug effects / Q000378:metabolism*; D011756:Diphosphates / Q000494:pharmacology; D010064:Embryo Implantation / Q000502:physiology; D005260:Female; D005990:Glycerol / Q000031:analogs & derivatives / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D010920:Placenta / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D049368:Receptors, Lysophosphatidic Acid / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D055988:Uterine Artery / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D011756:Diphosphates; D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D042461:Vascular Endothelial Growth Factor A; C408642:diacylglycerol pyrophosphate; D016753:Interleukin-10; D040281:Vascular Endothelial Growth Factor Receptor-1; D005990:Glycerol; C032881:lysophosphatidic acid