title: Heparin exerts anti-apoptotic effects on uterine explants by targeting the endocannabinoid system.
abstract: Miscarriage caused by Gram-negative bacteria infecting the female genital tract is one of the most common complications of human pregnancy. Intraperitoneal administration of LPS to 7-days pregnant mice induces embryo resorption after 24 h. Here, we show that LPS induced apoptosis on uterine explants from 7-days pregnant mice and that CB1 receptor was involved in this effect. On the other hand, heparin has been widely used for the prevention of pregnancy loss in women with frequent miscarriage with or without thrombophilia. Besides its anticoagulant properties, heparin exerts anti-inflammatory, immunomodulatory and anti-apoptotic effects. Here, we sought to investigate whether the administration of heparin prevented LPS-induced apoptosis in uterine explants from 7-days pregnant mice. We found that heparin enhanced cell survival in LPS-treated uterine explants and that this effect was mediated by increasing uterine FAAH activity. Taken together, our results point towards a novel mechanism involved in the protective effects of heparin.
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, Buenos Aires, Argentina.
authors.forename: Ana Inés
authors.initials: AI
authors.lastname: Salazar
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, Buenos Aires, Argentina.|Biomedicine Research Institute of Buenos Aires, National Research Council, Partner Institute of the Max Planck Society, Buenos Aires, Argentina.
authors.forename: Claudia
authors.initials: C
authors.lastname: Vercelli
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, Buenos Aires, Argentina.
authors.forename: Victoria
authors.initials: V
authors.lastname: Schiariti
authors.affiliation: Institute for Pharmacological Research, National Research Council, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Carlos
authors.initials: C
authors.lastname: Davio
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, Buenos Aires, Argentina.
authors.forename: Fernando
authors.initials: F
authors.lastname: Correa
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, Buenos Aires, Argentina. anafranchi2000@gmail.com.
authors.forename: Ana María
authors.initials: AM
authors.lastname: Franchi
mesh_terms: D000022:Abortion, Spontaneous / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D010064:Embryo Implantation; D063388:Endocannabinoids / Q000378:metabolism*; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism; D014599:Uterus / Q000378:metabolism*
chemical_list: D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1; D006493:Heparin
keywords: Cell survival; Endocannabinoid system; FAAH; Miscarriage; Pregnancy loss