Differential expression of endocannabinoid system in normal and preeclamptic placentas: Effects on nitric oxide synthesis

Abán, Cyntia; Leguizamón, Gustavo; Cella, Maximiliano; Damiano, Alicia E.; Franchi, A.M.; Farina, Mariana

doi:10.1016/j.placenta.2012.10.009

Cited by 40 publications

(44 citation statements)

References 45 publications

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“…Therefore, decreased serum concentration of anandamide in preeclampsia might be a consequence of its sequestration in the placenta by binding to syncytiotrophoblasts overexpressing CB1. Nevertheless, Aban et al 38 detected similar CB1 protein expression in normal and preeclamptic placental tissues.…”

Section: Discussionmentioning

confidence: 96%

Decreased circulating anandamide levels in preeclampsia

et al. 2015

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The endocannabinoid system has a key role in female reproduction, including implantation, decidualization and placentation. A growing number of studies indicate that placental and peripheral blood anandamide levels correlate closely with both spontaneous miscarriage and ectopic pregnancy. Anandamide has also been implicated in blood pressure regulation. In this study, we aimed to determine circulating anandamide levels in preeclampsia for the first time in the literature. Forty-three preeclamptic patients and 71 healthy pregnant women were involved in this case-control study. Serum anandamide concentrations were determined by high-performance liquid chromatography-mass spectrometry technique. Serum total soluble fms-like tyrosine kinase-1 (sFlt-1) and biologically active placental growth factor (PlGF) levels were measured by electrochemiluminescence immunoassay. For statistical analyses, nonparametric methods were applied. Serum levels of anandamide were significantly lower in preeclamptic patients than in healthy pregnant women (0.75 (0.44-1.03) ng ml(-1) vs. 1.30 (0.76-2.0) ng ml(-1), P<0.001). Preeclamptic patients had significantly higher sFlt-1 levels (12,121 (7963-18,316) pg ml(-1) vs. 2299 (1393-3179) pg ml(-1), P<0.001) and significantly lower PlGF concentrations (71.2 (39.2-86.4) pg ml(-1) vs. 256.8 (181.1-421.0) pg ml(-1), P<0.001) as compared with healthy pregnant women. Serum anandamide concentrations did not correlate with serum levels of sFlt-1 and PlGF in our healthy pregnant and preeclamptic groups. In conclusion, we demonstrated for the first time in the literature that serum anandamide concentrations are decreased in women with preeclampsia. However, the cause and consequence of this observation remain to be determined.

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Section: Discussionmentioning

confidence: 96%

Decreased circulating anandamide levels in preeclampsia

et al. 2015

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“…More recently, contrary to FAAH, NAPE-PLD expression was shown to be significantly higher in preeclamptic than in normal placentas, though no differences were observed in CB1 expression [98]. It was also hypothesized that AEA has an important implication in the normal function of placental tissues by modulating nitric oxide synthase (NOS) activity.…”

Section: Endocannabinoid System During Placental Developmentmentioning

confidence: 99%

“…In fact, it was observed that AEA modulates rat NO placental levels by two independent pathways: by stimulating NO synthesis via TRPV1 or diminishing the NOS activity via cannabinoid receptors, which depends on the production of cyclooxygenase-2 derivatives [85, 99]. Since placental villous from women with preeclampsia presented amplified NOS activity, increased AEA levels may be due to higher NAPE-PLD expression [98]. …”

Section: Endocannabinoid System During Placental Developmentmentioning

confidence: 99%

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

Fonseca

Correia-da-Silva

Almada

et al. 2013

International Journal of Endocrinology

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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.

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“…Thus, AEA and 2-AG act as endogenous ligands for cannabinoid receptors. 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 .…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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Increased vascular sensitivity to Ang II is a marker of a hypertensive human pregnancy. Recent evidence of interactions between the RAS and the endocannabinoid system (ECS) suggests that anandamide (AEA) and 2-arachidonoylglycerol (2-AG) may modulate Ang II contraction. We hypothesized that these interactions may contribute to the enhanced vascular responses in hypertensive pregnancy. We studied Ang II contraction in isolated uterine artery (UA) at early gestation in a rat model that mimics many features of preeclampsia, the transgenic hAGN×hREN (TgA), and control Sprague-Dawley (SD) rats. We determined the role of the cannabinoid receptor CB1 by blockade with SR171416A, and the contribution of AEA and 2-AG degradation to Ang II contraction by inhibiting their hydrolyzing enzymes FAAH (with URB597) or MAGL (with JZL184) respectively. TgA UA showed increased maximal contraction and sensitivity to Ang II that was inhibited by indomethacin. FAAH blockade decreased Ang IIMAX in SD UA, and decreased both Ang IIMAX and sensitivity in TgA UA. MAGL blockade had no effect on SD UA and decreased Ang IIMAX and sensitivity in TgA UA. Blockade of the CB1 receptor in TgA UA had no effect. Immunolocalization of FAAH and MAGL showed a similar pattern between groups; FAAH predominantly localized in endothelium and MAGL in smooth muscle cells. We demonstrated an increased Ang II contraction in TgA UA before initiation of the hypertensive phenotype. AEA and 2-AG reduced Ang II contraction in a CB1-independent manner. These RAS-ECS interactions may contribute to the enhanced vascular reactivity in early stages of hypertensive pregnancy.

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Differential expression of endocannabinoid system in normal and preeclamptic placentas: Effects on nitric oxide synthesis

Cited by 40 publications

References 45 publications

Decreased circulating anandamide levels in preeclampsia

Decreased circulating anandamide levels in preeclampsia

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

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

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