Hipoxia inducible factor 1 (HIF-1) impairs fusión of human trophoblast BeWo cells: influence of endocannabinoid signaling

DAMIANO, ALICIA; FARINA, MARIANA; MARTÍNEZ, NORA; ABÁN, CYNTIA; ETCHEVERRY, TOMÁS

CABA

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

SAIC, SAFIS, SAI, SAIB, SAB, SAB, SAA, SAH, SAP

The syncytiotrophoblast (STB) form a multinucleated layer that is maintained and regenerated by the fusion of underlying cytotrophoblast cells (CTBs). This structure is responsible for specialized functions of the human placenta and disturbance in this process may result in pregnancy-associated diseases such as preeclampsia and intrauterine growth restriction. Hypoxia modifies human placental villous syncytialization, however these mechanisms remains unknown. Previously we demonstrated that hypoxia inducible factor-1 alpha (HIF-1α) deregulated the endocannabinoid system (ES) in human placenta. In the present study, we investigated if HIF-1 and ES perform pivotal roles in trophoblast syncytialization.BeWo cell line was cultured with 100µM forskolin (FSK) to induce cell fusion. CTB (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. The location of the E-cadherin was studied by immunocytochemistry. Incubation with CoCl2 and Met-AEA significantly reduced cell viability (p