title: Lipopolysaccharide-induced murine embryonic resorption involves changes in endocannabinoid profiling and alters progesterone secretion and inflammatory response by a CB1-mediated fashion.
abstract: Genital tract infections are a common complication of human pregnancy that can result in miscarriage. We have previously shown that a lipopolysaccharide (LPS) induces embryonic resorption in a murine model of inflammatory miscarriage. This is accompanied by a dramatic decrease in systemic progesterone levels associated with a robust pro-inflammatory response that results in embryo resorption. Here, we tested the hypothesis that the endogenous cannabinoid system (eCS), through cannabinoid receptor 1 (CB1), plays a role in regulating progesterone levels and, therefore, the pro-inflammatory response. We show that LPS treatment in pregnant mice causes significant changes in the eCS ligands, which are reversed by progesterone treatment. We further show the CB1-KO mice maintain higher plasma progesterone levels after LPS treatment, which is associated with a feebler uterine inflammatory response and a significant drop in embryo resorption. These data suggest that manipulation of CB1 receptors and/or ligands is a potential therapeutic avenue to decrease infection-induced miscarriage.
authors.affiliation: Laboratory of Physiopathology of Pregnancy and Labor, Center for Pharmacological and Botanical Studies, National Research Council, School of Medicine, University of Buenos Aires, Argentina. Electronic address: manuwolfson@gmail.com.
authors.forename: Manuel L
authors.initials: ML
authors.lastname: Wolfson
authors.affiliation: Laboratory of Physiopathology of Pregnancy and Labor, Center for Pharmacological and Botanical Studies, National Research Council, School of Medicine, University of Buenos Aires, Argentina.
authors.forename: Fernando
authors.initials: F
authors.lastname: Correa
authors.affiliation: Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Leishman
authors.affiliation: Biomedicine Research Institute of Buenos Aires, Partner Institute of the Max Planck Society (MPSP), National Research Council, Ciudad Autónoma de Buenos Aires (CABA), Buenos Aires, Argentina.
authors.forename: Claudia
authors.initials: C
authors.lastname: Vercelli
authors.affiliation: Laboratory of Molecular Endocrinology, Center for Pharmacological and Botanical Studies, National Research Council, School of Medicine, University of Buenos Aires, Argentina.
authors.forename: Cora
authors.initials: C
authors.lastname: Cymeryng
authors.affiliation: Laboratory of Physiopathology of Pregnancy and Labor, Center for Pharmacological and Botanical Studies, National Research Council, School of Medicine, University of Buenos Aires, Argentina.
authors.forename: Julieta
authors.initials: J
authors.lastname: Blanco
authors.affiliation: Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA.
authors.forename: Heather B
authors.initials: HB
authors.lastname: Bradshaw
authors.affiliation: Laboratory of Physiopathology of Pregnancy and Labor, Center for Pharmacological and Botanical Studies, National Research Council, School of Medicine, University of Buenos Aires, Argentina.
authors.forename: Ana María
authors.initials: AM
authors.lastname: Franchi
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020964:Embryo Loss / Q000139:chemically induced / Q000378:metabolism*; D063388:Endocannabinoids / Q000378:metabolism*; D005260:Female; D008070:Lipopolysaccharides; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism*; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D063388:Endocannabinoids; D008070:Lipopolysaccharides; D043884:Receptor, Cannabinoid, CB1; D011374:Progesterone
keywords: CB1 knockout; Decidua; Embryotoxicity; Endocannabinoid system