HYPOXIA-REOXYGENATION IN THE PHYSIOPATHOLOGY OF THE PLACENTA: ALTERATION OF THE ENDOCANNABINOID SYSTEM AND TROPHOBLAST SYNCYTIALIZATION

ETCHEVERRY TOMAS; MARTÍNEZ NORA; FARINA MARIANA

CIUDAD DE BUENOS AIRES

Congreso; Reunion Anual de Sociedades de Biociencias; 2023

The placenta is a highly specialized transient organ. Within this tissue, different types of cells interact and function in synergy//a coordinated manner, providing a unique microenvironment. The cytotrophoblast (CTB) is a mononucleated cell capable of proliferating, differentiating, and fusing, giving rise to the syncytiotrophoblast (STB), the outer multinucleated layer that covers the chorionic villi. This process, known as syncytialization, begins from implantation and continues until the end of pregnancy, as the STB is continuously and highly relatedly renewed by the underlying CTB. Disruption of this process can lead to pregnancy-associated diseases. Preeclampsia (PE) is a severe pregnancy complication characterized by arterial hypertension, proteinuria, and damage to several organs. It is postulated that placental ischemia-reperfusion contributes to its development, triggering inflammation, oxidative stress, and endothelial dysfunction. The STB, responsible for maternal-fetal exchange in the placenta, is affected in PE, with alterations detected in the syncytialization process. //and abnormalities in the syncytialization process were detected. In this pathological condition, we have demonstrated alterations in several components of the endocannabinoid system (ECS). Endocannabinoids are a family of lipid signaling molecules that regulate physiological processes, being anandamide (AEA) one of the most relevant endocannabinoids. In our laboratory, we have shown an increase in cannabinoid receptor 1 (CB1) and the enzyme NAPEPLD, the main pathway for anandamide synthesis, as well as a decrease in fatty acid amide hydrolase (FAAH), the enzyme responsible for anandamide hydrolysis, in preeclamptic placentas. We investigated the role of hypoxia- reoxygenation (HR) as a model of damage in PE and demonstrated that normal placentas subjected to HR show alterations in ECS components similar to those observed in pathological conditions, suggesting that changes in oxygen tension could be responsible for the detected alterations in pathological conditions. We evaluated the syncytialization process and demonstrated that both HR and stabilization of hypoxia inducible factor (HIF-1α) disrupt trophoblast fusion and differentiation. Additionally, we assessed the impact of the ECS and observed that an increase in AEA tone deregulates syncytialization. Taken together, the results obtained allow us to postulate that HR events, which placentas may undergo during pregnancy complications such as preeclampsia, could alter ECS expression and deregulate the syncytialization process, contributing to a deficiency in placental functionality.