scholarly journals The fundamental role of the endocannabinoid system in endometrium and placenta: implications in pathophysiological aspects of uterine and pregnancy disorders

2020 ◽  
Vol 26 (4) ◽  
pp. 586-602 ◽  
Author(s):  
J Maia ◽  
BM Fonseca ◽  
N Teixeira ◽  
G Correia-da-Silva
Keyword(s):  
Endometrial Cancer ◽  
Ectopic Pregnancy ◽  
Fallopian Tube ◽  
Biological Activities ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Metabolic Enzymes ◽  
Current Evidence ◽  
Original Research

Abstract BACKGROUND The endocannabinoid system (ECS) consists of the cannabinoid receptors CB1 and CB2, the main endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and their metabolic enzymes N-acylphosphatidylethanolamine-specific phospholipase D, fatty acid amide hydrolase, diacylglycerol lipase and monoacylglycerol lipase. This system is involved in the modulation of essential physiological processes. Its role in the reproductive system has become significantly important in recent years, given its major role in events such as gametogenesis, decidualisation, implantation and placentation. OBJECTIVE AND RATIONALE In this paper, we review the literature and summarize the role of the ECS elements in reproduction and their potential as early markers for diagnosis of reproductive disorders or as pharmacological targets for treatment. SEARCH METHODS Original research and review papers published from 1964 to June 2019 were selected in terms of relevance, reliability and quality by searching PubMed, MEDLINE and Web of Science, using the following search terms: endocannabinoid system and endometriosis; endocannabinoid system and ectopic pregnancy; endocannabinoid system and miscarriage; endocannabinoid system and pre-eclampsia; endocannabinoid system and endometrial cancer; endocannabinoid system and reproduction; endocannabinoid, endometrium; placenta; N-acylethanolamines; anandamide; 2-arachidonoylglycerol; and cannabinoids. OUTCOMES This review demonstrates relevant information concerning ECS alterations in endometriosis, ectopic pregnancy, miscarriage, pre-eclampsia and endometrial cancer. We highlight the importance of the endocannabinoids in endometrial and placental physiology and pathophysiology, from studies in vitro and in vivo and in clinical observations. The most studied of the endogenous cannabinoids is AEA. The levels of AEA were increased in plasma of patients with endometriosis and miscarriage, as well as in the fallopian tube of women with ectopic pregnancy and in endometrial biopsies of endometrial cancer. Changes in the pattern of expression of the cannabinoid receptor CB1 were also observed in endometrial biopsies of endometriosis, fallopian tube and decidua of patients with ectopic pregnancy and pre-eclamptic placenta. Moreover, alterations in CB2 expression have been reported in association with endometrial cancer. In general, studies on the cannabinoid signalling through CB2 and on the biological activities of the other major endocannabinoid, namely 2-AG, as well as its metabolic enzymes are scarce and avidly required. WIDER IMPLICATIONS The pathophysiological mechanisms involved in the described endometrial and placental pathologies are still unclear and lack the means for an early diagnosis. Based on current evidence, though alterations in ECS are demonstrated at tissue level, it is difficult to associate plasmatic changes in AEA with specific endometrial and placental diseases. Thus, pairing alterations in AEA levels with 2-AG and/or other endocannabinoid-like molecules may provide more accurate and early diagnoses. In addition, patients may benefit from new therapies that target the ECS and endocannabinoid signalling.

scholarly journals Elevated Brain Fatty Acid Amide Hydrolase Induces Depressive-Like Phenotypes in Rodent Models: A Review

2021 ◽  
Vol 22 (3) ◽  
pp. 1047
Author(s):  
Dorsa Rafiei ◽  
Nathan J. Kolla
Keyword(s):  
Depressive Symptoms ◽  
Fatty Acid ◽  
Animal Models ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Animal Models Of Depression ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Altered activity of fatty acid amide hydrolase (FAAH), an enzyme of the endocannabinoid system, has been implicated in several neuropsychiatric disorders, including major depressive disorder (MDD). It is speculated that increased brain FAAH expression is correlated with increased depressive symptoms. The aim of this scoping review was to establish the role of FAAH expression in animal models of depression to determine the translational potential of targeting FAAH in clinical studies. A literature search employing multiple databases was performed; all original articles that assessed FAAH expression in animal models of depression were considered. Of the 216 articles that were screened for eligibility, 24 articles met inclusion criteria and were included in this review. Three key findings emerged: (1) FAAH expression is significantly increased in depressive-like phenotypes; (2) genetic knockout or pharmacological inhibition of FAAH effectively reduces depressive-like behavior, with a dose-dependent effect; and (3) differences in FAAH expression in depressive-like phenotypes were largely localized to animal prefrontal cortex, hippocampus and striatum. We conclude, based on the animal literature, that a positive relationship can be established between brain FAAH level and expression of depressive symptoms. In summary, we suggest that FAAH is a tractable target for developing novel pharmacotherapies for MDD.

scholarly journals Role of pelvic and para-aortic lymphadenectomy in endometrial cancer: Current evidence

2014 ◽  
Vol 40 (2) ◽  
pp. 301-311 ◽  
Author(s):  
Giorgio Bogani ◽  
Sean C. Dowdy ◽  
William A. Cliby ◽  
Fabio Ghezzi ◽  
Diego Rossetti ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Current Evidence

scholarly journals The Role of Radiotherapy in Endometrial Cancer: Current Evidence and Trends

2011 ◽  
Vol 13 (6) ◽  
pp. 472-478 ◽  
Author(s):  
Carien L. Creutzberg ◽  
Remi A. Nout
Keyword(s):  
Endometrial Cancer ◽  
Current Evidence

scholarly journals A Molar Pregnancy within the Fallopian Tube

2016 ◽  
Vol 2016 ◽  
pp. 1-3 ◽  
Author(s):  
Laura Allen ◽  
Charlotte Dawson ◽  
Patricia Nascu ◽  
Tyler Rouse
Keyword(s):  
Ectopic Pregnancy ◽  
Fallopian Tube ◽  
Spontaneous Abortion ◽  
Postoperative Care ◽  
Vaginal Bleeding ◽  
Adnexal Mass ◽  
First Trimester ◽  
Molar Pregnancy ◽  
Rare Occurrence

Background. Discussion of the incidence of molar pregnancy and ectopic pregnancy. Role of salpingostomy and special considerations for postoperative care.Case. The patient is a 29-year-old G7P4 who presented with vaginal bleeding in the first trimester and was initially thought to have a spontaneous abortion. Ultrasound was performed due to ongoing symptoms and an adnexal mass was noted. She underwent uncomplicated salpingostomy and was later found to have a partial molar ectopic pregnancy.Conclusion. This case illustrates the rare occurrence of a molar ectopic pregnancy. There was no indication of molar pregnancy preoperatively and this case highlights the importance of submitting and reviewing pathological specimens.

Abnormalities in neuroendocrine stress response in psychosis: the role of endocannabinoids

2015 ◽  
Vol 46 (1) ◽  
pp. 27-45 ◽  
Author(s):  
E. Appiah-Kusi ◽  
E. Leyden ◽  
S. Parmar ◽  
V. Mondelli ◽  
P. McGuire ◽  
...  
Keyword(s):  
Stress Response ◽  
Hpa Axis ◽  
Psychotic Disorders ◽  
Endocannabinoid System ◽  
Current Evidence ◽  
Response To Stress ◽  
Health And Disease ◽  
Stress Response System ◽  
Precise Role

The aim of this article is to summarize current evidence regarding alterations in the neuroendocrine stress response system and endocannabinoid system and their relationship in psychotic disorders such as schizophrenia. Exposure to stress is linked to the development of a number of psychiatric disorders including psychosis. However, the precise role of stress in the development of psychosis and the possible mechanisms that might underlie this are not well understood. Recently the cannabinoid hypothesis of schizophrenia has emerged as a potential line of enquiry. Endocannabinoid levels are increased in patients with psychosis compared with healthy volunteers; furthermore, they increase in response to stress, which suggests another potential mechanism for how stress might be a causal factor in the development of psychosis. However, research regarding the links between stress and the endocannabinoid system is in its infancy. Evidence summarized here points to an alteration in the baseline tone and reactivity of the hypothalamic–pituitary–adrenal (HPA) axis as well as in various components of the endocannabinoid system in patients with psychosis. Moreover, the precise nature of the inter-relationship between these two systems is unclear in man, especially their biological relevance in the context of psychosis. Future studies need to simultaneously investigate HPA axis and endocannabinoid alterations both at baseline and following experimental perturbation in healthy individuals and those with psychosis to understand how they interact with each other in health and disease and obtain mechanistic insight as to their relevance to the pathophysiology of schizophrenia.

Mitochondria: a possible nexus for the regulation of energy homeostasis by the endocannabinoid system?

2014 ◽  
Vol 307 (1) ◽  
pp. E1-E13 ◽  
Author(s):  
Christopher Lipina ◽  
Andrew J. Irving ◽  
Harinder S. Hundal
Keyword(s):  
Energy Homeostasis ◽  
Endocannabinoid System ◽  
Oxidative Capacity ◽  
Current Evidence ◽  
Peripheral Insulin Resistance ◽  
Physiological Processes ◽  
Peripheral Stimulation ◽  
The Metabolic Syndrome ◽  
Lipid Utilization

The endocannabinoid system (ECS) regulates numerous cellular and physiological processes through the activation of receptors targeted by endogenously produced ligands called endocannabinoids. Importantly, this signaling system is known to play an important role in modulating energy balance and glucose homeostasis. For example, current evidence indicates that the ECS becomes overactive during obesity whereby its central and peripheral stimulation drives metabolic processes that mimic the metabolic syndrome. Herein, we examine the role of the ECS in modulating the function of mitochondria, which play a pivotal role in maintaining cellular and systemic energy homeostasis, in large part due to their ability to tightly coordinate glucose and lipid utilization. Because of this, mitochondrial dysfunction is often associated with peripheral insulin resistance and glucose intolerance as well as the manifestation of excess lipid accumulation in the obese state. This review aims to highlight the different ways through which the ECS may impact upon mitochondrial abundance and/or oxidative capacity and, where possible, relate these findings to obesity-induced perturbations in metabolic function. Furthermore, we explore the potential implications of these findings in terms of the pathogenesis of metabolic disorders and how these may be used to strategically develop therapies targeting the ECS.

scholarly journals An update of Wnt signalling in endometrial cancer and its potential as a therapeutic target

2018 ◽  
Vol 25 (12) ◽  
pp. R647-R662 ◽  
Author(s):  
A Coopes ◽  
C E Henry ◽  
E Llamosas ◽  
C E Ford
Keyword(s):  
Endometrial Cancer ◽  
Therapeutic Target ◽  
Treatment Options ◽  
Wnt Signalling ◽  
Current Evidence ◽  
Gynaecological Malignancy ◽  
Genomic Analyses ◽  
Developed Nations ◽  
Multiple Tumour

Endometrial cancer is the most common gynaecological malignancy in developed nations, and its prevalence is rising as women defer or decide not to have children and as obesity rises, both key risk factors. Despite this, treatment options remain limited, particularly for advanced or refractory disease. New genomic analyses have revealed distinct mutational profiles with therapeutic and prognostic potential. Wnt signalling, which is pivotal in embryogenesis, healing and homeostasis, is of importance in the endometrium and has been linked to carcinogenesis. This review aims to update and discuss the current evidence for the role of β-catenin dependent and independent Wnt signalling, including the ROR receptors in the endometrium and its potential as a therapeutic target, in light of recent trials of Wnt-targeted therapy in multiple tumour types.

scholarly journals New Perspectives on the Use of Cannabis in the Treatment of Psychiatric Disorders

Medicines ◽  
2018 ◽  
Vol 5 (4) ◽  
pp. 107 ◽  
Author(s):  
Maria Scherma ◽  
Paolo Masia ◽  
Matteo Deidda ◽  
Walter Fratta ◽  
Gianluigi Tanda ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Therapeutic Target ◽  
Endocannabinoid System ◽  
Present Review ◽  
Current Evidence ◽  
Anxiety And Depression ◽  
Beneficial Effects ◽  
Pathological Conditions

Following the discovery of the endocannabinoid system and its potential as a therapeutic target for various pathological conditions, growing interest led researchers to investigate the role of cannabis and its derivatives for medical purposes. The compounds Δ9-tetrahydrocannabinol and cannabidiol are the most abundant phytocannabinoids found in cannabis extracts, as well as the most studied. The present review aims to provide an overview of the current evidence for their beneficial effects in treating psychiatric disorders, including schizophrenia, anxiety, and depression. Nevertheless, further investigations are required to clarify many pending issues, especially those relative to the assessment of benefits and risks when using cannabis for therapeutic purposes, thereby also helping national and federal jurisdictions to remain updated.

scholarly journals Role of endocannabinoid system in pressure natriuresis, in mice with and without fatty acid amide hydrolase

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Ashfaq Ahmad ◽  
Sara K. Dempsey ◽  
Zdravka Daneva ◽  
Ningjun Li ◽  
Pin‐Lan Li ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Amide Hydrolase ◽  
Pressure Natriuresis ◽  
Fatty Acid Amide
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