IJUP08 - Universidade do Porto

Spatio-temporal characterization of the Endocannabinoid System
enzymes-FAAH and COX-2 in the fetoplacental unit
A. Leite 1 , B. Fonseca 1,2 , N.A. Teixeira 1,2 and G. Correia da Silva 1,2
1Laboratory of Biochemistry, Faculty of Pharmacy, University of Porto, Portugal.
2 IBMC- Institute of Molecular and Cellular Biology, University of Porto, Portugal.
The comprehension of the mechanisms underlying the effects caused by the consumption
of Cannabis sativa was essential for the discovery of an endogenous complex signalling
system – the endocannabinoid system. Anandamide (AEA), the main endocannabinoid
(EC), which mimics the action of exogenous cannabinoids, was the first ligand to be
discovered and is able to bind to the cannabinoid receptors CB1, CB2 and to the vanilloid
receptor VR1. AEA is locally released from its phospholipid precursor by a Nacylphosphatidylethanolamine
(NAPE)-specific phospholipase D (NAPE-PLD) and the
levels of AEA are regulated by its inactivation namely via a fatty acid amide hydrolase
(FAAH) and a cyclooxygenase (COX-2).
Previous studies have demonstrated that the components of this system are important for
the maintenance of the low endocannabinoid levels necessary for the correct blastocyst
implantation [1]. However, little is known on the physiological significance of AEA during
fetoplacental development. Therefore, using the rat as the model for haemochorial
placentation, we examined the spatiotemporal expression patterns of FAAH and COX-2 by
immunohistochemistry and Western blot on days 8, 10, 12, 14, 16 and 19 of the gestational
period.
The results demonstrate the presence of FAAH and COX-2 in maternal tissues, namely in
decidual cells and in NK cells, during the process of decidual remodelling and placental
development, decreasing its expression throughout pregnancy. Therefore, the expression of
the enzymes responsible for the inactivation of endocannabinoids associated with the
presence of CB and VR1 receptors in decidual cells suggests a relevant role for this system
during placental development.
The study of the expression of the enzymes and receptors involved in the regulation of this
system becomes clinically relevant, since the EC present dual functionality, that is, when
expressed in low levels they perform their physiological regulatory functions, whereas its
deregulation and inherent high levels of these ligands are associated with spontaneous
pregnancy loss. At this point it is mandatory to remember that the consumption of
Cannabis (which uses the same metabolism such as EC) during pregnancy may alter de
enzymatic expression in addition to the endocannabinoid levels, consequently, originating
a series of pregnancy dysfunctions as a result of abnormal and non-functional placental
development. Therefore, the endocannabinoid system may be a potential important target
concerning human infertility.
References:
[1] Wang, H., Xie, H., Sun, X., Kingsley, J.P., Lawrence, J., Cravatt, B.F. and Dey, S.K. (2007),
Differential regulation of endocannabinoid synthesis and degradation in the uterus during embryo
implantation, Prostaglandins & Other Lipid Mediators, 83, 62–74.
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