1. Lipopolysaccharide-induced murine embryonic resorption involves changes in endocannabinoid profiling and alters progesterone secretion and inflammatory response by a CB1-mediated fashion.
- Author
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Wolfson ML, Correa F, Leishman E, Vercelli C, Cymeryng C, Blanco J, Bradshaw HB, and Franchi AM
- Subjects
- Animals, Disease Models, Animal, Embryo Loss chemically induced, Female, Mice, Mice, Knockout, Pregnancy, Receptor, Cannabinoid, CB1 genetics, Embryo Loss metabolism, Endocannabinoids metabolism, Lipopolysaccharides, Progesterone metabolism, Receptor, Cannabinoid, CB1 metabolism
- 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., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2015
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