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

Abstract

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.

Decreased circulating anandamide levels in preeclampsia

“…[2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] Endocannabinoids are endogenous ligands that bind to the similar receptor as delta-9-tetrahydrocannabinol (Δ 9 -THC), the most potent psychotropic constituent of marijuana. The most studied endocannabinoid is N-arachidonoylethanolamine (also known as anandamide), which is reported to have a central role in female reproduction, particularly in decidualization, 17 oviductal transport, 18 preimplantation embryo development, 19 timely embryo implantation and ensuring receptive uterine environment. 20 Tightly regulated anandamide levels are critical for reproductive success, which are accomplished through on-demand enzyme synthesis by the N-acylphosphatidylethanolamine-specific phospholipase D and degradation via fatty acid amide hydrolase (FAAH).…”

Increased Angiotensin II Contraction of the Uterine Artery at Early Gestation in a Transgenic Model of Hypertensive Pregnancy Is Reduced by Inhibition of Endocannabinoid Hydrolysis

“…Endocannabinoids possess vasoactive, mitogenic, and differentiating properties, and are implicated in placentation 9 and in several pregnancy disorders including preeclampsia 10 . Endocannabinoids participate in the regulation of angiogenesis during implantation and decidualization 11 , control myometrial contractility 12 , and regulate uterine and umbilical blood flow 13 . All these events are determinants of a successful pregnancy and may have devastating consequences when altered 14 .…”

Endocannabinoids

“…NAPE-PLD, that is chemically and enzymatically distinct from other known PLDs, is a member of the β-lactamase family of zinc-metal hydrolases, is highly conserved in mouse, rat and human, is stimulated by calcium, is highly expressed in the brain as well as in kidney, spleen, lung, heart and liver and is involved in the formation of other, cannabinoid-receptor inactive, N-acyl-ethanolamines (C16:0, C18:0 and C18:1) (Petersen and Hansen 1999; Ueda et al 2001a;Liu et al 2002;). Interestingly, studies performed using NAPE-PLD knockout mice suggested that while an increase in endogenous levels of NAPEs with saturated and monounsaturated N-acyl chains was observed, few or no changes were observed in the levels of polyunsaturated NAPEs and NAEs, thus suggesting the existence of alternative AEA biosynthetic pathways (Brown et al 2013;Cascio 2013;Fonseca et al 2013). There is evidence too that: (1) AEA is formed from N-acyl-lysophosphatidylethanolamine by a lysophospholipase-D-enzyme (lyso-PLD) (Sun et al 2004) (Fig.…”