Role of the endocannabinoid system in the mechanisms involved in the LPS-induced preterm labor.
Prematurity is the leading cause of perinatal morbidity and mortality worldwide. There is a strong causal relationship between infection and preterm births. Intrauterine infection elicits an immune response involving the release of inflammatory mediators like cytokines and prostaglandins (PG) that trigger uterine contractions and parturition events. Anandamide (AEA) is an endogenous ligand for the cannabinoid receptors CB1 and CB2. Similarly to PG, endocannabinoids are implicated in different aspects of reproduction, such as maintenance of pregnancy and parturition. Little is known about the involvement of endocannabinoids on the onset of labor in an infectious milieu. Here, using a mouse model of preterm labor induced by lipopolysaccharide (LPS), we explored changes on the expression of components of endocannabinoid system (ECS). We have also determined whether AEA and CB antagonists alter PG production that induces labor. We observed an increase in uterine N-acylphosphatidylethanolamine-specific phospholipase D expression (NAPE-PLD, the enzyme that synthesizes AEA) upon LPS treatment. Activity of catabolic enzyme fatty acid amide hydrolase (FAAH) did not change significantly. In addition, we also found that LPS modulated uterine cannabinoid receptors expression by downregulating Cb2 mRNA levels and upregulating CB1 protein expression. Furthermore, LPS and AEA induced PGF2a augmentation, and this was reversed by antagonizing CB1 receptor. Collectively, our results suggest that ECS may be involved in the mechanism by which infection causes preterm birth.
María Victoria
MV
Bariani
Ana Paula
AP
Domínguez Rubio
Maximiliano
M
Cella
Laboratory of Physiopathology of Pregnancy and LaborCenter for Pharmacological and Botanical Studies, National Research Council, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina andLaboratory of PhysiopathogenyDepartment of Physiology, School of Medicine, University of Buenos Aires, Argentina.
Juliana
J
Burdet
Ana María
AM
Franchi
Julieta
J
Aisemberg
D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D015237:Dinoprost / Q000378:metabolism; D004195:Disease Models, Animal; D063388:Endocannabinoids / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D005865:Gestational Age; D008070:Lipopolysaccharides; D008807:Mice, Inbred BALB C; D007752:Obstetric Labor, Premature / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014599:Uterus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001095:Arachidonic Acids; D063387:Cannabinoid Receptor Antagonists; D015237:Dinoprost; D063388:Endocannabinoids; D008070:Lipopolysaccharides; D010739:Phospholipase D; D053284:Polyunsaturated Alkamides; D011374:Progesterone; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D000099252:Fatty Acid Amide Hydrolases; C578453:CNR1 protein, mouse; C571431:Cnr2 protein, mouse; C482199:lipopolysaccharide, E coli O55-B5; C506062:Napepld protein, mouse; C078814:anandamide