Morphological and Electrical Properties of Human Trophoblast Choriocarcinoma, BeWo Cells

Ramos, A.J.; Cantero, M.R.; Zhang, P.; Raychowdhury, M.K.; Green, A.; MacPhee, D.; Cantiello, H.F.

doi:10.1016/j.placenta.2008.02.013

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Volume 29, Issue 6 , Pages 492-502, June 2008

Morphological and Electrical Properties of Human Trophoblast Choriocarcinoma, BeWo Cells

A.J. Ramos
- Nephrology Division and Electrophysiology Core, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA
M.R. Cantero
- Instituto de Investigaciones Cardiológicas (ININCA) UBA-CONICET, Buenos Aires, Argentina
P. Zhang
- Nephrology Division and Electrophysiology Core, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA
M.K. Raychowdhury
- Nephrology Division and Electrophysiology Core, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA
A. Green
- Department of Reproductive/Developmental Biology, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada
D. MacPhee
- Department of Reproductive/Developmental Biology, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada
H.F. Cantiello
- Nephrology Division and Electrophysiology Core, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA
- Instituto de Investigaciones Cardiológicas (ININCA) UBA-CONICET, Buenos Aires, Argentina
- Corresponding author. Nephrology Division and Electrophysiology Core, MGH East, Building 149, 13th Street, Charlestown, MA 02129, USA. Tel.: +1 617 726 5640; fax: +1 617 726 5669.

Accepted 27 February 2008. published online 17 April 2008.

Abstract

The syncytiotrophoblast of the human placenta arises from fusion of stem cells called cytotrophoblasts. The molecular mechanisms associated with cell fusion and syncytiation of cytotrophoblastic cells remain largely unknown. In the present study, we investigated the morphological and electrical properties of BeWo cells, a human choriocarcinoma-derived trophoblast cell model, with several features of the human cytotrophoblast. Cultured cells tended to cluster, but only fused into small, multinucleated syncytia in the presence of cAMP (72h). The morphological features of both the actin and microtubular cytoskeletons indicated that within 72h of constant exposure to cAMP, intracellular cortical actin cytoskeleton disappeared, which was the most prominent inducing factor of multi-nucleation. The presence of the cation channel protein, polycystin-2 (PC2), a TRP-type cation channel, associated with placental ion transport in term human syncytiotrophoblast, co-localised with acetylated tubulin in midbodies, but was found non-functional under any conditions. Different electrical phenotypes were observed among control BeWo cells, where only 26% (8 of 31 cells) displayed a voltage-dependent outwardly rectifying conductance. Most quiescent BeWo cells had, however, a low, slightly outwardly rectifying basal whole cell conductance. Acute exposure to intracellular cAMP (<15min) increased the whole cell conductance by 122%, from 0.72nS/cell to 1.60nS/cell, and eliminated the voltage-regulated conductance. The encompassed evidence indicates that the early events in BeWo cell fusion and syncytiation occur by cAMP-associated changes in ionic conductance but not morphological changes associated to chronic exposure to the second messenger. This suggests a tight regulation, and important contribution of cation conductances in cytotrophoblastic cells prior to syncytiation.