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Preeclampsia (PE) was first reported thousands of years ago, yet there is still a shortage of biomarkers to determine the severity and type of PE. The importance of the expanded endocannabinoid system, or endocannabinoidome (eCBome), has emerged recently in placental physiology and pathology, though the potential alterations of the eCBome in PE have not been fully explored. Analysis by qRT‐PCR using placental samples of normotensive and PE women demonstrate for the first time the presence of ABHD4, GDE1, and DAGLβ in both normotensive and PE placental tissues. Interestingly, NAPE‐PLD, FAAH‐1, DAGLα, MAGL, and ABHD6 mRNA levels were increased in the placental tissues of PE patients. Quantification in plasma and placental tissues showed a decrease for anandamide (AEA), N‐oleoylethanolamine (OEA), and N‐docosahexaenoylethanolamine (DHEA) in the placenta, accompanied only by a decrease in plasma levels of AEA. In addition, a strong negative correlation was obtained between OEA and the biomarker of PE, soluble fms‐like tyrosine kinase‐1. Given the inflammatory nature of PE and the anti‐inflammatory role of OEA and DHEA, the decrease in the local levels of these mediators may underlie the inflammatory component of this pathology. Additionally, lower AEA levels in both placenta and plasma may contribute to the atypical alterations of the spiral arteries in PE due to the vasorelaxation effects of AEA. These results add new information to the role of the eCBome members in placental development, while also pointing to a potential role as biomarkers of PE. [ABSTRACT FROM AUTHOR]

The endocannabinoid system has evolved as a key regulator in several pathological and physiological processes, including placentation, decidualization and implantation. In addition, it is known that Cannabis and cannabinoids negatively affect female reproduction. Although, the biological action of synthetic cannabinoids, such as WIN-55,212, in human fertility and pregnancy outcome remain to be unveiled. A tight balance between proliferation, differentiation and apoptosis of trophoblast cells is required for placental development and pregnancy outcome. Therefore, in this work, the effects of the synthetic cannabinoid WIN-55,212 in placental cytotrophoblast cells were explored. For that, it was used a human choriocarcinoma cell line, BeWo cells, and primary cultures of human cytotrophoblasts isolated from term placentas. Results demonstrate that this synthetic cannabinoid induces cell cycle arrest. We also observed that cell viability loss was associated with a disruption of mitochondrial membrane potential and activation of caspases -9 and -3/-7 independently of reactive oxygen species (ROS) production or recruitment of the endoplasmic reticulum stress marker CHOP . Moreover, these effects were prevented by pre-incubation with a selective cannabinoid receptor 1 (CBR1) antagonist (AM281). Thus, our results provide strong evidences of the apoptotic process induced by WIN-55,212 through the activation of the CBR1, which may reveal the impact of cannabinoids consumption during placental development. [ABSTRACT FROM AUTHOR]