SYNCYTIALIZATION OF HUMAN TROPHOBLAST IS INFLUENCED BY ENDOCANNABINOID SIGNALING

ETCHEVERRY T; MARTINEZ NORA; DAMIANO ALICIA; ABAN C; FARINA M

Buenos Aires

Congreso; IV Congreso Internacional de Medicina Translacional; 2018

The trophoblast of human placenta forms a syncytium in direct contact with maternal blood. The syncytiotrophoblast (STB) is the main structural and functional epithelial layer required for normal fetal growth and development. Hypoxia inhibit human placental villous syncytialization, however the exact mechanisms remain unknown. Disturbance in this process may result in pregnancy-associated diseases such as preeclampsia and intrauterine growth restriction. Endogenous cannabinoids (endocannabinoids, ECs) are an emerging group of bioactive lipids mediators which, together with their receptors and the enzymes involved in their metabolism, constitute the endocannabinoid system (ES). One of the most important endocannabinoids produced by the placenta is anandamide (N-arachidonylethanoalmine, AEA). In the present study, we investigated if the endocannabinoid system participates in the impairment of trophoblast syncytialization induced by hypoxia inducible factor 1 (HIF-1).BeWo cell line was cultured with 25µM forskolin (FSK) to induce cell fusion. Cytothophoblast (BeWo) and STB (BeWo + FSK) cells were treated with and without cobalt chloride (CoCl2), a hypoxia-mimetic agent that stabilizes (HIF-1α); or R-(+)-Methanandamide (Met-AEA), a stable anandamide analogous. Cell viability was evaluated by MTT assay. Markers for trophoblast syncytialization: syncytin-1 and glial cells missing-1 (GCM-1), were analyzed by western blot and RT-PCR, respectively. The distribution of the E-cadherin was studied by immunocytochemistry.Incubation with CoCl2 and Met-AEA significantly reduced cell viability (p