Endocannabinoid Signaling Directs Periimplantation Events

Abstract

An emerging concept in female reproduction is the role of endocannabinoids, a group of endogenously produced lipid mediators that bind to and activate cannabinoid receptors. Although adverse effects of cannabinoids in female reproduction have been implicated for years, the mechanisms by which they exert these effects remained elusive. With the identifi cation of cannabinoid receptors, endocannabinoid ligands, their key synthetic and hydrolytic pathways, and the generation of knockout mouse models for cannabinoid receptors, a wealth of information is now available regarding the signifi cance of cannabinoid/endocannabinoid signaling in early pregnancy. This review focuses on various aspects of endocannabinoid signaling in preimplantation embryo development and activation, and uterine differentiation during the periimplantation embryouterine dialog. It is hoped that a deeper understanding will lead to potential clinical applications of the endocannabinoid system as a target for regulating female fertility.K EYWORDS: cannabinoid/endocannabinoid , embryo deve lopment , embryo oviductal transport , implantation , mouse

Dynamics of expression and localization of the cannabinoid system in granulosa cells during oocyte nuclear maturation

“…The regulation of ''AEA tone'' by FAAH has been proposed as an important event in the oviduct during early pregnancy (33), as well as in blastocyst activation (34) and implantation (35), but no hypotheses have been proposed in relation to such a process in oocyte maturation. Even so, it has been described that AEA concentration in human follicular fluid rises during oocyte maturation (15) and that the concentration is even higher in the oviduct than in follicular fluid (36).…”

Preimplantation Mouse Embryo Is a Target for Opioid Ligand-Receptor Signaling1

“…For example, previous studies have demonstrated that cannabinoid signaling participates in sperm-egg fertilization, preimplantation development of embryos and their timely transport from the oviduct into the uterus, and embryo-uterine cross-talk during implantation and decidualization [52][53][54][55][56]. Opioid receptors and cannabinoid receptors are all belong to the G-protein-coupled receptors super families.…”

Histomorphometric evaluation of cannabinoid receptor and anandamide modulating enzyme expression in the human endometrium through the menstrual cycle

“…Plasma AEA levels are maintained by the actions of the enzymes fatty acid amide hydrolase (FAAH) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) and together with a putative, but yet undiscovered anandamide membrane transporter, constitute the major components of the 'endocannabinoid system' (Di Marzo 2008;Habayeb et al 2008a;Pacher et al 2006). All of these component parts of the endocannabinoid system have been demonstrated in rodent uteri (Paria et al 2001;Wang et al 2006bWang et al , 2007, suggesting that the endocannabinoid system is intimately involved in the physiology of mammalian reproduction. Also, in rodent models of early pregnancy, it has been demonstrated that the expression of FAAH and NAPE-PLD are modulated by circulating sex steroid hormones (Maccarrone et al 2000a) and by the presence of the blastocyst ) such that FAAH levels are increased and NAPE-PLD levels are decreased in the implantation site as compared to the nonimplantation site (Guo et al 2005;Maccarrone 2009), whilst at the same time elevated local anandamide levels are associated with detrimental effects on the mouse blastocyst (Sun and Dey 2008).…”