title: Effects of Sildenafil Citrate and Heparin Treatments on Placental Cell Morphology in a Murine Model of Pregnancy Loss.
abstract: Lipopolysaccharide (LPS) injections during pregnancy are well established as models for pregnancy complications, including fetal growth restriction (FGR), thrombophilia, preterm labor and abortion. Indeed, inflammation, as induced by LPS injection has been described as a pivotal factor in cases of miscarriage related to placental tissue damage. The phosphodiesterase-5 inhibitor sildenafil (Viagra®) is currently used to treat FGR cases in women, while low-molecular weight heparin (Fragmin®) is a standard treatment for recurrent miscarriage (RM). However, the pathways and cellular dynamics involved in RM are not completely understood. The aim of this study was to evaluate the protective effect of sildenafil and dalteparin in a mouse model of LPS-induced abortion. Histopathology, ultrastructural analysis and immunofluorescence for P-selectin were studied in two different placental cell types: trophoblast cells and labyrinth endothelial cells. Treatment with sildenafil either alone or in combination with heparin showed the best response against LPS-induced injury during pregnancy. In conclusion, our results support the use of these drugs as future therapeutic agents that may protect the placenta against inflammatory injury in RM events. Analyses of the ultrastructure and placental immunophysiology are important to understand the mechanism underlying RM. These findings may spark future studies and aid in the development of new therapies in cases of RM.
authors.affiliation: Ultrastructure Laboratory, Aggeu Magalhx00E3;es Research Center, Oswaldo Cruz Foundation, Recife, Brazil.
authors.forename: Rayana Leal
authors.initials: RL
authors.lastname: Luna
authors.forename: Anne Gabrielle
authors.initials: AG
authors.lastname: Vasconcelos
authors.forename: Ana Karolina Santana
authors.initials: AK
authors.lastname: Nunes
authors.forename: Wilma Helena
authors.initials: WH
authors.lastname: de Oliveira
authors.forename: Karla Patricia de Sousa
authors.initials: KP
authors.lastname: Barbosa
authors.forename: Christina Alves
authors.initials: CA
authors.lastname: Peixoto
mesh_terms: D000026:Abortion, Habitual / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D017985:Dalteparin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D010920:Placenta / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000473:pathology*; D011247:Pregnancy; D000068677:Sildenafil Citrate / Q000627:therapeutic use*; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D000925:Anticoagulants; D008070:Lipopolysaccharides; D058986:Phosphodiesterase 5 Inhibitors; D000068677:Sildenafil Citrate; D017985:Dalteparin