Elevated Anandamide and Related<i>N</i>-Acylethanolamine Levels Occur in the Peripheral Blood of Women With Ectopic Pregnancy and Are Mirrored by Changes in Peripheral Fatty Acid Amide Hydrolase Activity

Gebeh, Alpha K.; Willets, Jonathon M.; Bari, Monica; Hirst, Robert A.; Marczylo, Timothy H.; Taylor, Anthony H.; Maccarrone, Mauro; Konje, Justin C.

doi:10.1210/jc.2012-3390

Cited by 30 publications

(24 citation statements)

References 39 publications

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“…FAAH activity is not limited to AEA; however, and has been shown to metabolize all of the NAEs [28]. Much less is known about the role of 2-AG in the regulation of pregnancy; however, it as also been shown to be regulated in the uterus as a function of the ovarian cycle [29] Therefore, the interplay between progesterone and the eCS is complex and not fully understood [14; 15; 23–25]. …”

Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide-induced murine embryonic resorption involves changes in endocannabinoid profiling and alters progesterone secretion and inflammatory response by a CB1-mediated fashion

Wolfson

Correa

Leishman

et al. 2015

Molecular and Cellular Endocrinology

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Genital tract infections are a common complication of human pregnancy that can result in miscarriage. We have previously shown that a lipopolysaccharide (LPS) induces embryonic resorption in a murine model of inflammatory miscarriage. This is accompanied by a dramatic decrease in systemic progesterone levels associated with a robust pro-inflammatory response that results in embryo resoprtion. Here, we tested the hypothesis that the endogenous cannabinoid system (eCS), through cannabinoid receptor 1 (CB1), plays a role in regulating progesterone levels and, therefore, the pro-inflammatory response. We show that LPS treatment in pregnant mice causes significant changes in the eCS ligands, which are reversed by progesterone treatment. We further show the CB1-KO mice maintain higher plasma progesterone levels after LPS treatment, which is associated with a feebler uterine inflammatory response and a significant drop in embryo resorption. These data suggest that manipulation of CB1 receptors and/or ligands is a potential therapeutic avenue to decrease infection-induced miscarriage.

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Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide-induced murine embryonic resorption involves changes in endocannabinoid profiling and alters progesterone secretion and inflammatory response by a CB1-mediated fashion

Wolfson

Correa

Leishman

et al. 2015

Molecular and Cellular Endocrinology

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“…25 High maternal peripheral blood endocannabinoid levels modulated by low FAAH activity in lymphocytes can inhibit successful pregnancy after in vitro fertilization, 26,27 and were recently associated with ectopic pregnancy possibly through tubal dysfunction. 28 Endocannabinoids have also been implicated in blood pressure regulation. 29 Endocannabinoids can cause vasodilation through CB1, TRPV1 and nitric oxide (NO)-mediated or NO-independent mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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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“…Recently, Cui et al [95, 96] found reduced FAAH expression in the endometrium of patients with PCOS and an increase in AEA plasma levels, as FAAH is mainly involved in AEA degradation. Previous studies have shown that elevated plasma AEA levels in connection with a lower FAAH activity resulted in ectopic pregnancy which is also linked to PCOS [85, 97]. Thus, it seems likely that a dysregulation of the ECS is involved in pregnancy complications of women with PCOS.…”

Section: The Ecs In Gynecological Disorders and Cancermentioning

confidence: 99%

Cannabinoids in Gynecological Diseases

Luschnig

Schicho

2019

Med Cannabis Cannabinoids

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The endocannabinoid system (ECS) is a multifunctional homeostatic system involved in many physiological and pathological conditions. The ligands of the ECS are the endocannabinoids, whose actions are mimicked by exogenous cannabinoids, such as phytocannabinoids and synthetic cannabinoids. Responses to the ligands of the ECS are mediated by numerous receptors like the classical cannabinoid receptors (CB1 and CB2) as well as ECS-related receptors, e.g., G protein-coupled receptors 18 and 55 (GPR18 and GPR55), transient receptor potential ion channels, and nuclear peroxisome proliferator-activated receptors. The ECS regulates almost all levels of female reproduction, starting with oocyte production through to parturition. Dysregulation of the ECS is associated with the development of gynecological disorders from fertility disorders to cancer. Cannabinoids that act at the ECS as specific agonists or antagonists may potentially influence dysregulation and, therefore, represent new therapeutic options for the therapy of gynecological disorders.

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Elevated Anandamide and RelatedN-Acylethanolamine Levels Occur in the Peripheral Blood of Women With Ectopic Pregnancy and Are Mirrored by Changes in Peripheral Fatty Acid Amide Hydrolase Activity

Abstract: Elevated endocannabinoid levels and reduced FAAH activity are associated with ectopic pregnancy and may modulate tubal function, suggesting dysfunctional endocannabinoid action in ectopic implantation. Oleoylethanolamide may play a critical role in embryo-tubal transport.

Cited by 30 publications

References 39 publications

Lipopolysaccharide-induced murine embryonic resorption involves changes in endocannabinoid profiling and alters progesterone secretion and inflammatory response by a CB1-mediated fashion

Lipopolysaccharide-induced murine embryonic resorption involves changes in endocannabinoid profiling and alters progesterone secretion and inflammatory response by a CB1-mediated fashion

Decreased circulating anandamide levels in preeclampsia

Cannabinoids in Gynecological Diseases

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