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Anandamide interferes with human endometrial stromal-derived cell differentiation: An effect dependent on inhibition of cyclooxygenase-2 expression and prostaglandin E2 release.
Biofactors. 2016 May; 42(3):277-86.B

Abstract

The 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.

Authors+Show Affiliations

UCIBIO, REQUIMTE, Biological Sciences Department, Laboratory of Biochemistry, Faculty of Pharmacy, University of Porto, Porto, Portugal.LAQV, REQUIMTE, Chemical Sciences Department, Laboratory of Bromatology and Hydrology, Faculty of Pharmacy, University of Porto, Porto, Portugal.UCIBIO, REQUIMTE, Biological Sciences Department, Laboratory of Biochemistry, Faculty of Pharmacy, University of Porto, Porto, Portugal.UCIBIO, REQUIMTE, Biological Sciences Department, Laboratory of Biochemistry, Faculty of Pharmacy, University of Porto, Porto, Portugal.Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale Delle Ricerche, Pozzuoli, (NA), Italy.Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale Delle Ricerche, Pozzuoli, (NA), Italy.UCIBIO, REQUIMTE, Biological Sciences Department, Laboratory of Biochemistry, Faculty of Pharmacy, University of Porto, Porto, Portugal.UCIBIO, REQUIMTE, Biological Sciences Department, Laboratory of Biochemistry, Faculty of Pharmacy, University of Porto, Porto, Portugal.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26945481

Citation

Almada, Marta, et al. "Anandamide Interferes With Human Endometrial Stromal-derived Cell Differentiation: an Effect Dependent On Inhibition of Cyclooxygenase-2 Expression and Prostaglandin E2 Release." BioFactors (Oxford, England), vol. 42, no. 3, 2016, pp. 277-86.
Almada M, Cunha S, Fonseca BM, et al. Anandamide interferes with human endometrial stromal-derived cell differentiation: An effect dependent on inhibition of cyclooxygenase-2 expression and prostaglandin E2 release. Biofactors. 2016;42(3):277-86.
Almada, M., Cunha, S., Fonseca, B. M., Amaral, C., Piscitelli, F., Di Marzo, V., Correia-da-Silva, G., & Teixeira, N. (2016). Anandamide interferes with human endometrial stromal-derived cell differentiation: An effect dependent on inhibition of cyclooxygenase-2 expression and prostaglandin E2 release. BioFactors (Oxford, England), 42(3), 277-86. https://doi.org/10.1002/biof.1270
Almada M, et al. Anandamide Interferes With Human Endometrial Stromal-derived Cell Differentiation: an Effect Dependent On Inhibition of Cyclooxygenase-2 Expression and Prostaglandin E2 Release. Biofactors. 2016;42(3):277-86. PubMed PMID: 26945481.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anandamide interferes with human endometrial stromal-derived cell differentiation: An effect dependent on inhibition of cyclooxygenase-2 expression and prostaglandin E2 release. AU - Almada,Marta, AU - Cunha,Sara, AU - Fonseca,Bruno M, AU - Amaral,Cristina, AU - Piscitelli,Fabiana, AU - Di Marzo,Vincenzo, AU - Correia-da-Silva,Georgina, AU - Teixeira,Natércia, Y1 - 2016/03/04/ PY - 2015/11/14/received PY - 2016/01/21/accepted PY - 2016/3/7/entrez PY - 2016/3/8/pubmed PY - 2017/1/24/medline KW - UPLC-MS/MS KW - decidualization KW - endocannabinoids KW - prostaglandins SP - 277 EP - 86 JF - BioFactors (Oxford, England) JO - Biofactors VL - 42 IS - 3 N2 - The 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. SN - 1872-8081 UR - https://www.unboundmedicine.com/medline/citation/26945481/Anandamide_interferes_with_human_endometrial_stromal_derived_cell_differentiation:_An_effect_dependent_on_inhibition_of_cyclooxygenase_2_expression_and_prostaglandin_E2_release_ L2 - https://doi.org/10.1002/biof.1270 DB - PRIME DP - Unbound Medicine ER -