Participation of endocannabinoid system in the pathophysiology of human placenta

C. ABAN; N. MARTÍNEZ,; T. ETCHEVERRY; A. TORO; A. SEYAHIAN; A. FRANCHI; G. LEGUIZAMÓN; D. TRIGUBO; A. DAMIANO; M. FARINA

Simposio; Latin American Society for Maternal Fetal Interaction and Placenta; 2017

Cannabis use during pregnancy has been associated with an increase risk of adverse birth outcomes suggesting that the endogenous ligands for cannabinoid receptors could have a significant influence on pregnancy complications. Endocannabinoids (ECs) are an important family of lipidsignalling molecules that act as endogenous ligands of cannabinoid receptors (CB1 and CB2). We previously reported an aberrant endocannabinoid system in placentas from preeclampsia. Preeclampsia is a multisystem syndrome that represents a major factor for maternal and perinatal morbid-mortality, and affects 7e10% of pregnancies. Lipids are the principal components of biological membranes and play essential roles in cellular function regulating important processes such as proliferation, apoptosis and cell migration. In the placenta, apoptosis is a homeostatic mechanism that participates in syncytialization. Increasing evidencedemonstrates the relevance of ECs and hypoxia as modulators of trophoblast cell turnover. Hypoxia inducible factor 1 (HIF-1) regulates the expression of a large number of genes including those involved in cell cycle arrest and apoptosis. HIF-1a was detected in trophoblast of human placentas and its expression is exacerbated in pathological conditions. We found that HIF-1a stabilization decreased fatty acid amide hydrolase FAAH mRNA and protein levels, critical regulator in the metabolic control of ECs levels in normal and pathological pregnancy. Our results suggest that changes in ECs levels might be contribute to the upregulation of apoptoticparameters by a mechanism that involves activation of CB1 receptor. Thus, we proposed that abnormal expression of endocannabinoide system might contribute to deregulate important pathway connected to the placentation process.