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, 2013, 510540

The Endocannabinoid System in the Postimplantation Period: A Role During Decidualization and Placentation


The Endocannabinoid System in the Postimplantation Period: A Role During Decidualization and Placentation

B M Fonseca et al. Int J Endocrinol.


Although the detrimental effects of cannabis consumption during gestation are known for years, the vast majority of studies established a link between cannabis consumption and foetal development. The complex maternal-foetal interrelationships within the placental bed are essential for normal pregnancy, and decidua definitively contributes to the success of this process. Nevertheless, the molecular signalling network that coordinates strategies for successful decidualization and placentation are not well understood. The discovery of the endocannabinoid system highlighted new signalling mediators in various physiological processes, including reproduction. It is known that endocannabinoids present regulatory functions during blastocyst development, oviductal transport, and implantation. In addition, all the endocannabinoid machinery was found to be expressed in decidual and placental tissues. Additionally, endocannabinoid's plasmatic levels were found to fluctuate during normal gestation and to induce decidual cell death and disturb normal placental development. Moreover, aberrant endocannabinoid signalling during the period of placental development has been associated with pregnancy disorders. It indicates the existence of a possible regulatory role for these molecules during decidualization and placentation processes, which are known to be particularly vulnerable. In this review, the influence of the endocannabinoid system in these critical processes is explored and discussed.


Figure 1
Figure 1
Schematic representation of the fetomaternal interface and potential adverse effects arising from deregulated endocannabinoid signalling based on rodents and human studies. Endometrial stromal cells differentiate into decidual cells, preparing uterine tissues for pregnancy, whereas the invading trophoblast cells critically regulate placental growth and function. All the physiological and molecular processes occurring during those periods are complex but highly organized. Endocannabinoids have reported to be involved in decidualization, implantation, and trophoblast differentiation and invasion. Aberrant endocannabinoid signalling (shown in yellow boxes) is reflected in compromised reprogramming of the endometrial stromal cells, implantation and placentation manifesting in ectopic pregnancy, intrauterine growth restriction, preeclampsia, miscarriage, and spontaneous abortion.
Figure 2
Figure 2
Schematic cartoon portraying the apoptotic signalling pathway triggered by anandamide (AEA) in rat decidual cells. AEA binds and activates the specific G-protein-coupled cannabinoid receptor 1 (CB1). The CB1 activation results in intracellular ceramide accumulation through de novo synthesis. This would lead to subsequent increase in phosphorylation of p38 mitogen-activated protein kinase cascade (p38-MAPK), which thus affects the mitochondrial pathway. It is followed by a drop in mitochondrial membrane potential (Δψm), caspase-3/-7 activation, and apoptosis of decidual cells. This CB1 activation mechanism is believed to play a role in decidual cell death, thus affecting uterine remodeling processes occurring during placentation.

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