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Abstract
Endocannabinoids are a group of lipid ligands, which alongside the cannabinoid receptors and the enzymes in charge of their synthesis and degradation, conform the endocannabinoid system (ECS). Anandamide (AEA) is one of the main endocannabinoids produced by the human placenta [1]. Its levels are regulated by synthesis and degradation by NAPE-PLD and FAAH enzymes, respectively [2]. It has been described that the ECS play different roles in human placentation, and alterations in this system are associated with placental pathologies [3]. Our lab has previously demonstrated that preeclamptic placenta express more NAPE-PLD protein and less FAAH protein and activity, suggesting an increase in AEA tone [4].
One of the main models proposed for the pathophysiology of preeclampsia is the damage by hypoxia-reoxygenation (H/R). Our aim was to investigate if H/R or HIF-1α could mimic the changes observed in the several components of the ECS in preeclampsia. Placental explants were obtained from elective cesarean term placentas. Explants under H/R showed higher NAPE-PLD mRNA levels, while the HIF-1α stabilization did not present any changes. In the case of FAAH, both conditions significantly diminished FAAH mRNA. In conclusion, H/R could mimic the changes observed in preeclamptic placentas.
[2] F. Fezza, C. De Simone, D. Amadio, M. Maccarrone, Fatty acid amide hydrolase: a gate-keeper of the endocannabinoid system, Subcell Biochem 49 (2008) 101-32.
[3] M.A. Costa, The endocannabinoid system: A novel player in human placentation, Reprod Toxicol 61 (2016) 58-67.
[4] C. Aban, G.F. Leguizamon, M. Cella, A. Damiano, A.M. Franchi, M.G. Farina, Differential expression of endocannabinoid system in normal and preeclamptic placentas: effects on nitric oxide synthesis, Placenta 34(1) (2013) 67-74.
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