Role of the endocannabinoid system in the mechanisms involved in the LPS-induced preterm labor

BARIANI MARIA VICTORIA; DOMINGUEZ RUBIO ANA PAULA; CELLA, MAXIMILIANO; BURDET, JULIANA; FRANCHI, ANA MARIA; AISEMBERG JULIETA

REPRODUCTION

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 2015 vol. 150 p. 463 - 472

1470-1626

Prematurity is the leading cause of perinatal morbidity and mortality worldwide. There is a strong causal relationship betweeninfection and preterm births. Intrauterine infection elicits an immune response involving the release of inflammatory mediators likecytokines and prostaglandins (PG) that trigger uterine contractions and parturition events. Anandamide (AEA) is an endogenousligand for the cannabinoid receptors CB1 and CB2. Similarly to PG, endocannabinoids are implicated in different aspects ofreproduction, such as maintenance of pregnancy and parturition. Little is known about the involvement of endocannabinoids onthe onset of labor in an infectious milieu. Here, using a mouse model of preterm labor induced by lipopolysaccharide (LPS), weexplored changes on the expression of components of endocannabinoid system (ECS). We have also determined whether AEA andCB antagonists alter PG production that induces labor. We observed an increase in uterine N-acylphosphatidylethanolaminespecificphospholipase D expression (NAPE-PLD, the enzyme that synthesizes AEA) upon LPS treatment. Activity of catabolicenzyme fatty acid amide hydrolase (FAAH) did not change significantly. In addition, we also found that LPS modulated uterinecannabinoid receptors expression by downregulating Cb2 mRNA levels and upregulating CB1 protein expression. Furthermore, LPSand AEA induced PGF2a augmentation, and this was reversed by antagonizing CB1 receptor. Collectively, our results suggest thatECS may be involved in the mechanism by which infection causes preterm birth.