Anandamide restricts uterine stromal differentiation and is critical for complete decidualization

Fonseca, Bruno M.; Correia-da-Silva, Georgina; Teixeira, Natércia

doi:10.1016/j.mce.2015.04.024

Cited by 21 publications

(15 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In rats, it was described previously that the metabolic enzymes expressed in decidual cells are the main controllers of eCB levels throughout pregnancy (Fonseca et al 2010). In addition, AEA induces apoptosis in rat primary decidual cell cultures (Fonseca et al 2013a, Almada et al 2015 and interferes with decidualization process (Fonseca et al 2015). Herein, a novel role for AEA as a modulator of human decidualization was proposed, through an effect on both endometrial stromal cell proliferation and differentiation.…”

Section: Discussionmentioning

confidence: 95%

“…eCBs modulate basic biological processes, including the choice between cell proliferation, death and differentiation (Fonseca et al 2013a). In the rat model, it has been demonstrated that AEA interferes with decidual cell turnover by inducing apoptosis (Fonseca et al 2013b) and limits uterine stromal cell differentiation (Fonseca et al 2015). Nevertheless, the underlying mechanisms that govern the process of human endometrial decidualization and the involvement of the eCBs in this process remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The endocannabinoid anandamide impairs in vitro decidualization of human cells

Almada¹,

Amaral²,

Diniz-da-Costa³

et al. 2016

Reproduction

View full text Add to dashboard Cite

Endocannabinoids (eCBs) are endogenous mediators that along with the cannabinoid receptors (CB1 and CB2), a membrane transporter and metabolic enzymes form the endocannabinoid system (ECS). Several eCBs have been discovered with emphasis on anandamide (AEA). They are involved in several biological processes such as energy balance, immune response and reproduction. Decidualization occurs during the secretory phase of human menstrual cycle, which involves proliferation and differentiation of endometrial stromal cells into decidual cells and is crucial for the establishment and progression of pregnancy. In this study, a telomerase-immortalized human endometrial stromal cell line (St-T1b) and non-differentiated primary cultures of human decidual fibroblasts from term placenta were used to characterize the ECS using immunoblotting and qRT-PCR techniques. It was shown that St-T1b cells express CB1, but not CB2, and that both receptors are expressed in HdF cells. Furthermore, the expression of fatty acid amide hydrolase (FAAH), the main degrading enzyme of AEA, increased during stromal cell differentiation. AEA inhibited cell proliferation, through deregulation of cell cycle progression and induced polyploidy. Moreover, through CB1 binding receptor, AEA also impaired cell differentiation. Therefore, AEA is proposed as a modulator of human decidualization. Our findings may provide wider implications, as deregulated levels of AEA, due to Cannabis sativa consumption or altered expression of the metabolic enzymes, may negatively regulate human endometrial stromal cell decidualization with an impact on human (in)fertility.Free Portuguese abstract: A Portuguese translation of this abstract is freely available at http://www.reproduction-online.org/content/152/4/351/suppl/DC1.

show abstract

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

The endocannabinoid anandamide impairs in vitro decidualization of human cells

Almada¹,

Amaral²,

Diniz-da-Costa³

et al. 2016

Reproduction

View full text Add to dashboard Cite

show abstract

“…Recently, we reported that the eCB AEA limits the process of rat stromal cell differentiation, possibly through COX-2 down-regulation [16]. Nonetheless, the potential eCB-PG crosstalk beneath the maternal endometrium was not disclosed.…”

Section: Discussionmentioning

confidence: 96%

“…Recently, it was shown that in rat decidual cells, AEA induced cell death through COX-2 oxidative metabolism [15]. On the other hand, in rats, it has also been reported that AEA limits the progression of the stromal differentiation process and that PGs are important mediators for the differentiation process [16]. The regulatory PG function in early human pregnancy events is not yet clear.…”

Section: Introductionmentioning

confidence: 99%

Anandamide interferes with human endometrial stromal‐derived cell differentiation: An effect dependent on inhibition of cyclooxygenase‐2 expression and prostaglandin E₂ release

et al. 2016

View full text Add to dashboard Cite

SummaryThe human endometrium undergoes cyclical growth, differentiation, and regression periods throughout the reproductive life. The process in which endometrial stromal cells proliferate and differentiate into decidual cells, named decidualization, prepares a receptive endometrium for implantation. Prostaglandins (PGs) and endocannabinoids (eCBs) are crucial mediators of this process. We have recently reported that the eCB anandamide (AEA) interferes with rat stromal cell differentiation, and on the other hand, PGs are also crucial for decidualization. Therefore, in this study, we analyzed the AEA levels, both in nondifferentiated and in decidualizing human endometrial stromal cells by liquid chromatography‐mass spectrometry, and investigated the impact of AEA on PG release and cyclooxygenase‐2 (COX‐2) expression in human endometrial stromal‐derived cell differentiation. For that, an ultra‐performance liquid chromatography‐mass spectrometry/mass spectrometry method to measure prostaglandin E2 (PGE2) and prostaglandin F2α in biological samples was developed and validated. We demonstrate that AEA levels in decidualizing cells are lower than those in nondifferentiated cells, whereas PGE2 levels and COX‐2 expression are up‐regulated. Thus, low AEA levels may be essential for the onset of decidualization. On the contrary, in AEA‐treated cells undergoing decidualization, a decrease of COX‐2 protein levels and PGE2 production, in a manner dependent on cannabinoid receptor 1 activation, was observed. Overall, these findings suggest that a deregulation of the intricate network that drives cell differentiation may compromise pregnancy and fertility. It is clinically relevant to understand the mechanisms that influence eCB and PG levels in the endometrium because they may shed light on the sequence of events that lead to a successful pregnancy. © 2016 BioFactors, 42(3):277–286, 2016

show abstract

“…The breakdown of fatty acids as a source of energy through the β‐oxidation pathway also contributes to decidualization . In addition, the biosynthesis of lipid‐based metabolites such as endocannabinoids and prostaglandins is required for this process . However, in most of these studies, the metabolic alteration was inferred by the change of enzyme expression levels and the dynamics of metabolites were actually not determined.…”

Section: Introductionmentioning

confidence: 99%

Integration of Transcriptomic and Metabolomic Data Reveals Enhanced Steroid Hormone Biosynthesis in Mouse Uterus During Decidualization

et al. 2017

View full text Add to dashboard Cite

It has been long recognized that decidualization is accompanied by significant changes in metabolic pathways. In the present study, we used the GC-TOF-MS approach to investigate the global metabolite profile changes associated with decidualization of mouse uterus on day 8 of pregnancy. We identified a total of 20 differentially accumulated metabolites, of which nine metabolites were down-regulated and 11 metabolites were up-regulated. As expected, seven differentially accumulated metabolites were involved in carbohydrate metabolism. We observed statistically significant changes in polyamines, putrescine and spermidine. Interestingly, the pantothenic acid, also known as vitamin B , was up-regulated. Finally, by integrating with transcriptomic data obtained by RNA-seq, we revealed enhanced steroid hormone biosynthesis during decidualization. Our study contributes to an increase in the knowledge on the molecular mechanisms of decidualization.

show abstract

Anandamide restricts uterine stromal differentiation and is critical for complete decidualization

Cited by 21 publications

References 33 publications

The endocannabinoid anandamide impairs in vitro decidualization of human cells

The endocannabinoid anandamide impairs in vitro decidualization of human cells

Anandamide interferes with human endometrial stromal‐derived cell differentiation: An effect dependent on inhibition of cyclooxygenase‐2 expression and prostaglandin E₂ release

Integration of Transcriptomic and Metabolomic Data Reveals Enhanced Steroid Hormone Biosynthesis in Mouse Uterus During Decidualization

Contact Info

Product

Resources

About

Anandamide restricts uterine stromal differentiation and is critical for complete decidualization

Cited by 21 publications

References 33 publications

The endocannabinoid anandamide impairs in vitro decidualization of human cells

The endocannabinoid anandamide impairs in vitro decidualization of human cells

Anandamide interferes with human endometrial stromal‐derived cell differentiation: An effect dependent on inhibition of cyclooxygenase‐2 expression and prostaglandin E2 release

Integration of Transcriptomic and Metabolomic Data Reveals Enhanced Steroid Hormone Biosynthesis in Mouse Uterus During Decidualization

Contact Info

Product

Resources

About

Anandamide interferes with human endometrial stromal‐derived cell differentiation: An effect dependent on inhibition of cyclooxygenase‐2 expression and prostaglandin E₂ release