Abstract
Prostaglandins (PG) are effective abortifacients and are important mediators of lipopolisaccharide (LPS)-induced embryonic resorption (ER). Besides, anandamide (AEA) has been described as one of the major endocannabinoids present in the uterus suggesting that it might play a role in reproduction. It has been reported that high levels of AEA are associated with pregnancy failure and that LPS increases AEA production. Also, it has been observed that AEA modulates PG production in different tissues. In this sense, we studied whether LPS-induced PG production is modulated by AEA and we also assessed the effect of this endocannabinoid on PG metabolism in an in vitro model. Uterine explants from BALB/c implantation sites were cultured in the presence of LPS plus cannabinoid receptor (CB) specific antagonists and PG production was assessed. Then, we studied the effect of exogenous AEA on different steps of PG metabolic pathway. We showed that AEA is involved in LPS-induced PG biosynthesis. Also, we observed that AEA exerts opposite effects on PGE2 and PGF2α biosynthesis, by inhibiting PGE2 production and increasing PGF2α levels. We suggest that AEA could be involved in the mechanisms implicated in LPS-induced ER. A better understanding of how AEA could be affecting ER could help developing specific interventions to prevent this pathology.
Highlights
Intrauterine infection plays a major role in the pathogenesis of early pregnancy loss
In the present study we investigated whether LPS-induced PG production is modulated by AEA and we determined the effect of this endocannabinoid on PG biosynthesis and catabolism in uterine explants from pregnant mice
To evaluate whether endogenous cannabinoids could modify LPSinduced PG production, uterine explants were incubated for 24 h in the presence of LPS (1 mg/ml), LPS plus AM251 (CB1 receptor antagonist) or LPS plus SR144528 (CB2 receptor antagonist) and prostaglandin E2 (PGE2) and prostaglandin F2a (PGF2a) levels were assessed by RIA
Summary
Intrauterine infection plays a major role in the pathogenesis of early pregnancy loss. Our previous results [1] showed that in vivo administration of lipopolysaccharide (LPS), a component of Gram-negative bacteria, increased prostaglandin E2 (PGE2) and prostaglandin F2a (PGF2a) production in the uterus of early pregnant mice. Anandamide (arachidonoylethanolamide, AEA) belongs to a group of endogenous lipids termed ‘‘endocannabinoids’’ [5] and is an agonist of type-1 (CB1) and type-2 (CB2) cannabinoid receptors. It has been described as one of the major endocannabinoids present in the uterus and this suggests that it might play a role in reproduction [6]. In the present study we investigated whether LPS-induced PG production is modulated by AEA and we determined the effect of this endocannabinoid on PG biosynthesis and catabolism in uterine explants from pregnant mice
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